^rs^vse 


(Enlbg*  of  ipijijstriatts  anb  &ttrgwma 


i&zfnma  Stbrarg 


EPIDEMIC  INFANTILE   PARALYSIS 

(heine-medin  disease) 


EPIDEMIC  INFANTILE  PARALYSIS 

(HEINE-MEDIN     DISEASE) 


BY- 
PROFESSOR    PAUL    H.    ROMER 

Principal  of  the  Institute  of  Hygiene  and  Experimental  Medicine  of  Marburg 


Translated  by 

H.    RIDLEY    PRENTICE,    M.B.,    B.S.Lond.,    M.R.C.P. 

Late  Resident  Medical  Officer  to  the  National  Hospital  for  the  Paralysed  and 

Epileptic,  Queen  Square 


With   57   Illustrations  in  the   Text 


NEW      YORK 

WILLIAM      WOOD      AND      COMPANY 

MDCCCCXIII 


J-VDG 


Translator's  Preface. 

It  appears  highly  probable  that  the  disease  known  as  Epidemic 
Infantile  Paralysis  will  become  more  and  more  menacing-  to  the 
community  in  England  as  well  as  in  other  countries.  In  its  sporadic 
form  the  disease  has  been  recognized  for  a  long  time;  its  effects  on 
isolated  lives  have  been  so  deplorable  that  it  has  come  to  be  regarded 
as  perhaps  the  most  feared  of  all  the  diseases  of  childhood.  But 
now  we  are  face  to  face  with  a  change  in  the  way  in  which  the  virus 
attacks  the  human  race ;  the  disease  has  become  epidemic  in  its 
incidence.  The  history  of  this  remarkable  disturbance  of  the 
balance  between  the  attack  of  the  virus  and  the  power  of  effective 
resistance  in  human  beings  is  told  in  the  present  book.  Written  as 
it  is  by  an  author  who  not  only  has  made  practical  use  of  the 
discovery  that  the  disease  is  communicable  to  monkeys,  but  also 
possesses  in  a  high  degree  the  sense  of  historical  perspective,  the 
book  contains  the  results  of  his  experimental  work,  and  describes 
fully  the  difficulties  which  have  stood  and  still  stand  in  the  way  of 
advance  in  the  elucidation  of  the  problems  presented  by  the  disease 
both  in  its  scientific  and  public  health  aspects.  Under  these  circum- 
stances it  appears  advisable  to  bring  the  work  within  reach  of  a 
larger  public  in  this  country. 

At  the  moment  of  going  to  press  the  report  on  the  Swedish 
epidemic  of  191 1  has  appeared;  it  marks  a  further  advance  in  the 
study  of  the  disease,  and  is  a  brilliant  vindication  of  the  claims  which 
Professor  Romer  has  put  forward  in  this  book  on  behalf  of  the 
experimental  method  of  investigation. 

London,  1913. 


a 


Digitized  by  the  Internet  Archive 

in  2010  with  funding  from 

Open  Knowledge  Commons 


http://www.archive.org/details/epidemicinfantilOOrm 


Pref 


ace. 

The  occurrence  of  cases  of  epidemic  infantile  paralysis,  the 
so-called  Heine-Medin  disease,  in  Marburg",  Hesse-Nassau,  gave  me 
the  opportunity  of  making  investigations  into  the  etiology  of  this 
disease.  A  considerable  portion  of  these  studies  has  already  been 
published,  in  the  form  of  short  articles,  in  the  Munchener  med. 
Wochenschrift,  and  in  communications  to  the  Medical  Society 
of  Marburg.  The  present  work  was  intended  originally  not  for 
publication,  but  merely  as  an  arrangement  of  the  various  above- 
mentioned  isolated  articles  and  lectures  in  a  definite  and  logical 
form.  As  the  work  proceeded,  however,  the  plan  became  wider, 
and  the  book  gradually  assumed,  its  present  form.  The  material 
itself  increased  in  two  directions. 

In  the  first  place  I  soon  recognized  that  the  collation  of  my  own 
humble  experimental  results  alone  would  give  but  a  feeble  repre- 
sentation of  the  stage  which  has  been  reached  in  the  study  of 
poliomyelitis.  Such  an  experience  must  fall  to  the  lot  of  any  experi- 
mental investigator  of  poliomyelitis  who  endeavours  to  give  form 
to  his  results  and,  in  so  doing,  makes  use  of  those  results  alone. 
This  may  be  easily  understood  when  one  considers,  that  so  far  the 
only  results  which  have  been  of  any  value  in  this  field  of  research 
have  depended  upon  the  use  of  monkeys,  and,  further,  that  the  cost 
of  procuring  and  keeping  these  animals  sets  very  definite  limits  to 
the  extent  of  the  investigation.  Consequently  I  was  obliged  to  make 
use  of  the  work  of  other  experimenters,  who  have  attacked  the 
problem  with  so  much  success  during  the  last  two  years,  in  order 
to  arrive  at  an  even  approximate  idea  of  the  present  state  of  the 
question. 

It  was  pointed  out  to  me  by  friends  that  a  review  of  the  present 
state  of  our  knowledge  would  be  of  interest  to  a  wider  public,  and 
in  carrying  out  this  idea  I  found  my  material  increasing  in  another 
direction.  The  experimental  work  not  only  involved  necessarily  a 
wide  study  of  the  literature,  but  threw  new  light  on  the  numerous 
previous  labours  undertaken  in  the  investigation  of  infantile 
paralysis.  I  have  endeavoured,  therefore,  to  bring  before  the  reader 
in  an  orderly  manner  the  mass  of  scattered  material  which  is  to  be 
found  in  the  literature  of  this  and  other  countries,  much  of  which 
is  accessible  only  with  difficulty.  In  starting  from  the  idea  that  a 
comprehensive  representation  of  the  development  of  our  knowledge 
of  Heine-Medin  disease  up  to  the  present  day  will  be  of  interest  to 
the  reader,  I  am  guided  by  my  own  experience.     In  the  summer  of 


viii  PREFACE 

1909,  when  reports  of  the  epidemic  occurrence  of  poliomyelitis  in 
Germany  appeared,  I  must  admit  that  the  disease  was  relatively  but 
little  known  to  me.  It  is  true  that,  from  the  time  when  I  was  a 
student,  the  classical  picture  of  infantile  paralysis,  as  described  in 
the  excellent  monograph  by  Heine,  was  known  to  me,  and  reports 
of  the  epidemic  occurrence  of  the  disease  had  reached  me  from  time 
to  time.  But,  as  easily  happens  when  one  is  not  immediately  con- 
cerned with  a  question,  I  had  not  realized  that  since  1890  our  concep- 
tion of  the  disease  had  altered  considerably  from  that  contained  in 
most  text-books.  Consequently,  when  the  epidemic  of  1909  once 
more  drew  attention  to  the  disease,  it  was  to  me  more  or  less  of  a 
novelty.  I  think  I  do  no  injustice  to  my  colleagues  in  the  profession 
if  I  assume  that  they  also  had  but  a  passing  acquaintance  with  the 
disease,  particularly  in  such  districts  where  it  had  not  assumed 
epidemic  proportions.  The  following  book,  therefore,  may  be 
perhaps  of  value;  the  more  so  as  it  seems  by  no  means  likely 
that  we  are  at  the  end  of  our  experience  of  this  particular  pest. 
The  latest  reports  from  Berlin  give  cause  for  the  fear  that  further 
outbreaks  are  to  be  expected. 

To  the  friendly  co-operation  of  Professor  Dr.  Eduard  Muller, 
the  Director  of  the  Medical  Polyclinic  in  this  town,  whose  clinical 
and  epidemiological  investigations  I  was  able  to  follow  step  by  step, 
and  to  supplement  along  experimental  lines,  I  owe  the  fact  that  I 
was  enabled  quickly  to  become  acquainted  with  the  clinical  picture, 
the  epidemiological  character  and  the  general  significance  of  the 
apparently  new  disease. 

In  the  following  pages  I  have  endeavoured  to  avoid  all  that 
savours  of  a  text-book;  they  form  a  resume  of  my  studies.  This 
has  been  all  the  easier  because,  in  spite  of  all  the  progress  which 
has  been  made,  there  are  still  so  many  obscure  points  in  the  disease, 
that  it  is  more  attractive  to  discuss  the  problems  which  remain  than 
to  lose  oneself  in  the  description  of  those  already  solved.  By 
always  drawing  attention  to  the  work  which  remains  to  be  done  I 
hope  that  I  have  succeeded  in  avoiding  the  tedium  which  attaches 
necessarily  to  a  book  which  is  made  up  largely  of  references.  If  I 
have  not  succeeded,  after  all.  I  ask  the  reader  not  to  take  the  will 
for  the  deed,  but  to  reckon  the  will  to  the  deed  in  my  favour. 

In  the  purely  experimental  part  of  this  work  I  have  had  the 
pleasure  of  the  extremely  intelligent  and  untiring  assistance  of 
Dr.  loseph.  the  present  assistant  in  the  bacteriological  department 
of  the  Hoechst  Dve  Works. 

P.  H.  Romer. 

Marburg. 


Contents. 


Chapter  I. 

The  Development  of  our  Knowledge  of  the  Nature  of 

the  Disease  of  Heine  and  Medin. 

Nomenclature,  p.   i — Historical  Retrospect,  p.  3. 

Chapter  II. 
The   Symptomatology   of   the   Disease   in   Man. 

PAGE 

I. — Historical     6 

The  period  before  Heine,  6— Heine's  work,  7 — From  Heine 
to  Medin,   10 — Medin  to  Wickman,    13. 

II. — The  Symptomatology  in  Man 13 

Period  of  incubation,  13 — Prodromal  symptoms,  13 — Stage  of 
paralysis,  14  (Abortive  type,  14;  Spinal  types,  15;  Type 
simulating  Landry's  disease,  17;  Bulbar  and  Pontine  types, 
18;  Cerebral  type,  18;  Ataxic  type,  iq;  Polyneuritic  type, 
19;  Aleningitic  type,  19) — Prognosis,  ig — Sporadic  infantile 
paralysis,  20. 

Chapter  III. 
Etiology  of  the   Disease. 

I. — Microscopical  and  Cultural  Researches  with  Experiments  on 

Animals  22 

The  older  views,  22 — Strumpell's  hypothesis,  23 — The  era  of 
cocci,  24- — The  accumulation  of  negative  results,  25 — Per- 
sonal bacteriological  research,  26 — Important  microscopical 
findings,  27 — Specific  intracellular  bodies,  29 — "  Cultures  of 
the  virus,"'  29 — Experiments  on  animals,  30. 

II. — Experimental     Research     ox     Poliomyelitis     in     Monkeys — 

Clinical  History  of  Experimental  Poliomyelitis 31 

Landsteiner's  original  experiment,  31 — Personal  experiments 
with  monkeys,  32 

[a]  Source  of  the  virus  used  in  my  experiments  ...  ...       34 

Susceptibility  of  monkeys  to  the  virus  of  poliomyelitis,  42. 

(b)  The  clinical  history  of  poliomyelitis  in  monkeys  ...         ...       43 

Period    of    incubation,     43 — Prodromal    symptoms,    44 — 

Stage  of  paralysis,  45  ((a)  Poliomyelitis  acutissima,  46; 
(b)  Poliomyelitis  acuta,  47;  [c)  Typical  spinal  para- 
lysis, 47;  (d)  Bulbar  and  Cerebral  forms,  49;  (e) 
Gastro-intestinal  symptoms,  54;  (/)  Abortive  forms, 
54;  (g)  Marasmic  forms,  56;  (h)  Recovery  from  the 
acute  stage,  57;  (i)  Recovery  from  the  paralysis,  S7 ', 
(k)  Relapses,  59) — Prognosis,  60. 


X  CONTENTS 

PAGE 

III. — The  Nature  of  the  Virus  ...        61 

Filtration  of  the  virus,  62 — Resistance  to  glycerine,  63 — The 
effect  of  low  and  high  temperatures,  65 — Resistance  to 
drying-,  66 — Behaviour  towards  disinfectants,  67 — The 
durability  of  the  virus  in  animals,  67 — The  effect  of  passing 
the  virus  through  animals,  68. 

IV. — The  Use  of  other  Animals  for  Experiments      69 

The  susceptibility  of  different  animals,  69 — Earlier  experi- 
ments with  rabbits,  70 — Krause  and  Meinicke's  experiments 
with  rabbits,  70 — Results  of  personal  experiments,  71 — 
Results  obtained  by  other  observers,  73 — Renewed  repetition 
of  the  experiments,  75 — Criticism  of  the  arguments  in  favour 
of  using  rabbits,  77 — Further  objections  to  experiments  with 
rabbits,  82 —An  attempt  to  explain  the  difference,  8^? — - 
Practical   conclusions,   84. 

Chapter  IV. 

Pathology   and    Pathogenesis. 

I. — Historical  Retrospect — The  Salient  Features     87 

Heine's  views,  87 — From  Heine  to  Charcot,  Roger  and 
Damaschinn,  89 — The  dispute  over  Charcot's  theory,  91  — 
Investigation  of  chronic  cases,  91 — Investigation  of  acute 
cases,  92 — Wickman's  investigations,  93 — More  recent  inves- 
tigators, 94. 

II. — The     Distribution    and    Spread    of    the    Virus    within    the 

Organism  94 

The    demonstration    of    the    virus    in    different    organs,    94 ;    in 
man,  95  ;  in  monkeys,  95 — Conclusions,  98 — The  methods  of  , 
inoculation,  gg — Attempts  to  determine  the  point  of  entrance 
of  the  virus,  101. 

III. — The  Pathological  Changes  found  in  Experimental  Polio- 
myelitis in  Monkeys  compared  with  those  found  in  Man  102 
Technique,  103 — Macroscopic  changes,  103 — Microscopic 
changes,  106  (Pia,  107;  Spinal  cord,  111;  Medulla  and  pons, 
120;  Brain,  122) — The  stage  of  repair,  125 — The  final 
stage,  127 — Poliomyelitis  in  adults,  Landry's  paralysis, 
polyneuritis,  rabies  and  Borna's  disease  in  their  relation  to 
Heine-Medin  disease,  128. 

IV. — Pathogenesis  '     ; 129 

The  point  of  attack  of  the  virus,  129 — The  spread  of  the  virus 
within  the  central  nervous  system,  132 — The  route  by- .which 
the  virus  reaches  the  spinal  cord,  133 — The  portal  of  entry 
of  the   virus,    134 — Conclusions,    135. 

Chapter  V. 
Epidemiology.' 

I. — History  of  the  Epidemics         136 

Early  reports,  136 — The  epidemics  in  the  different  countries 
(Sweden  and  Norway,  136;  Germany,  138;  Austria,  138; 
Holland  and  Switzerland,  139;  England,  139;  France,  139; 
Spain,  140;  Italy,  140;  Russia,  140;  North  America,  140; 
Cuba,  141  ;  Australia,  141) — The  origin  of  the  large 
epidemics,   141. 


CONTENTS  xi 

PAGE 

II. — The  Epidemiological  Characteristics  of  the  several  Outbreaks     142 
Season,     142 — Age,    sex,    predisposition,     142 — Proof    of    con- 
tagiousness, 144 — Confirmation  of  Wickman's  statements,  146. 

Chapter  VI. 

The  Fight  against  the   Disease. 

].— Immunity  and  Immunization      149, 

Clinical  and  epidemiological  experience,  148 — Attempts  to 
reinfect  monkeys,  151 — Methods  of  immunization  in  monkeys, 
156;  a)  Protective  inoculation  with  dry  virus,  156; 
(0)  Immunization  by  small  doses  of  virulent  material,  157; 
(7)  Immunization  with  virus  attenuated  or  killed  by  chemi- 
cal means,  158;  (8)  Immunization  with  heated  virus,  159; 
(e)  Immunization  with  mixtures  of  virus  and  serum  con- 
taining antibodies,  160;  (0  Immunization  during  the  incuba- 
tion period,  162;  (y)  The  biological  connection  between 
poliomyelitis  and  rabies  from  the  point  of  view  of  immunity, 
162. 

II. — Specific   Antibodies  162 

Fixation  of  complement,  162 — Specific  hypersensitiveness,  163 
— Successful  demonstration  of  antibodies,  163 — Serum  dia- 
gnosis, 166 — Serum  therapy,  171. 

III. — Experiments  with  Drugs  ..  -173 

IV. — Prophylaxis  ...         174 

Private  prophylaxis,   175 — State  regulation,    177. 

Conclusion 178 

Literature 180 

Index  igo, 


CHAPTER    I, 


The  Development  of  our  Knowledge  of  the 
Nature  of  the  Disease  of  Heine  and  Medin. 


-Jakob  v.  Heine,  who  gave  the  first  classical 
description  of  the  disease,  gave  it  the  name,  "  Spinal  Infantile 
Paralysis."  He  adopted  this  nomenclature  because  the  cases  which 
came  under  his  observation  were  either  children  or  adults  who  had 
been  stricken  with  the  disease  during  childhood;  further,  by  a  process 
of  deductive  reasoning  carried  out  with  great  analytical  clearness, 
he  was  convinced  that  the  site  of  the  lesion  must  be  in  the  spinal 
cord.  That  this  denomination  was  in  general  accurate  is  proved  by 
the  manner  in  which  this  name  of  the  disease,  which  he  was  the 
first  to  differentiate  as  a  clinical  entity,  has  been  preserved  even  to 
the  present  day.  An  attempt  was  made  by  the  French  writers  to 
give  currency  to  the  terms  "idiopathic"  or  "essential"  infantile 
paralysis;  but  even  at  a  time  when  the  site  of  the  lesion  was  not 
definitely  proved  these  terms  betrayed  themselves  as  mere  confes- 
sions of  ignorance,  and  they  rightly  disappeared  entirely  when  the 
spinal  origin  of  the  disease  was  clearly  demonstrated. 

When  knowledge  of  the  anatomical  distribution  of  the  funda- 
mental pathological  process  advanced,  a  more  exact  anatomical  term 
was  added  to  the  former  appellation,  in  accordance  with  the 
tendency  towards  an  anatomical  nomenclature  of  diseases  in  general, 
and  the  name  "  Poliomyelitis  Anterior  Acuta  "  was  coined,  which 
expressed  the  favourite  point  of  attack  of  the  disease. 

In  the  middle  of  the  'eighties  observations  on  groups  of  cases, 
in  a  few  instances  of  epidemics,  of  the  disease  began  to  accumulate, 
and  in  accordance  with  the  newly  gained  knowledge  the  names 
"Epidemic  Infantile  Paralysis"  and  "  Epidemic  Poliomyelitis"  came 
into  use.  But  when  Medin  proved  that  the  hypothesis  of  Strumpell 
and  Pierre  Marie  was  correct,  that  there  was  a  connection  between 
classical  infantile  paralysis  and  certain  forms  of  encephalitis,  these 
names  were  no  longer  satisfactory.  According  to  these  authors  the 
same  pathological  agent  may  produce  at  one  time,  by  affecting  the 
spinal  cord,  the  well-known  disease  described  in  a  masterly  manner 
by  v.  Heine,  at  another  time,  by  affecting  the  brain,  a  cerebral 
paralysis. 

I 


2  EPIDEMIC   INFANTILE   PARALYSIS 

In  spite  of  these  facts,  however,  the  old  term  "  Spinal  Infantile 
Paralysis  "  held  its  ground,  even  though  it  was  demonstrated  that 
not  infrequently  adults  were  attacked  by  the  disease.  The  name 
"  Paralysie  infantile,"  introduced  by  the  French  authors,  hereby  also 
lost  all  justification. 

There  were  three  reasons  why  the  name  "  Spinal  Infantile 
Paralysis  "  remained  without  a  rival,  besides  the  obvious  historical 
one,  vis.,  the  authority  of  v.  Heine.  In  the  first  place  it  was 
doubted  whether  a  disease  which  presented  so  constant  and  so 
definite  a  clinical  picture  as  spinal  paralysis  could  have  a  pathological 
cause  identical  with  a  disease  showing  such  a  remarkable  difference 
from  the  clinical  point  of  view  as  cerebral  paralysis.  Secondly,  it 
was  difficult  to  believe  that  a  disease,  which  appeared  to  be  a 
definite  system  disease  of  the  spinal  cord,  could  fall  out  of  its  role 
so  far  as  to  be  bound  to  no  system.  Pathological  investigation, 
which  took  place  usually  in  cases  of  long  standing  (owing  to  the 
fact  that  fatal  acute  cases  were  inaccurately  diagnosed),  showed 
that  the  site  of  the  lesion  corresponded  with  the  clinical  picture  and 
involved  practically  exclusively  the  grey  matter  of  the  anterior 
horns.  Finally,  the  absence  of  any  new,  accurate,  comprehensive, 
and  simple  term  led  to  the  retention  of  the  old,  even  though  it 
was  recognized  to  be  unsatisfactory. 

In  the  meanwhile  our  knowledge  of  the  histology  of  the  disease 
had  increased  and  changed;  investigation  of  recent  cases  had  shown 
that  lesions  were  to  be  found  in  the  medulla,  pons,  and  cerebrum, 
as  had  been  expected  by  the  more  acute  clinicians.  To  call  the 
disease  a  "  myelitis  "  was  unsatisfactory,  and  the  term  was  applicable 
to  only  a  fraction  of  the  cases.  After  Rissler,  Wickman,  v.  Harbitz 
and  Scheel  had  proved  that  the  disease  did  not  limit  itself  to  the 
grey  matter,  but  usually  involved  the  meninges  and  frequently  the 
white  matter  of  the  cord  and  brain,  the  term  "  poliomyelitis  "  was 
clearly  too  narrow.  These  results  having  been  confirmed  on  all 
hands,  an  attempt  was  made  to  give  expression  to  the  anatomical 
knowledge  thus  gained;  the  name  "  Meningo-myelo-encephalitis 
disseminata  "  was  evolved.  Besides  the  fact  that  such  a  name  could 
not  meet  with  general  use,  it  was  by  no  means  free  from  objections. 

It  is  to  the  credit  of  Wickman,  whose  work  we  shall  discuss 
more  fully  later,  that  he  drew  attention  to  cases  which  were  un- 
doubtedly caused  by  the  same  virus  as  the  cases  of  epidemic  infantile 
paralysis,  and  yet  showed  no  definite  signs  of  paralysis.  Clearly  it 
would  be  ridiculous  to  call  such  cases  paralysis;  the  term  polio- 
myelitis might  still  be  applicable  to  these  abortive  cases,  because 
it  appears  likely  that  some  degree  o'f  inflammation  of  the  grey 
matter  was  present;  yet  anatomically  this  has  not  been  clearly 
proved.  Wickman  found  a  way  out  of  these  manifold  difficulties. 
He  proposed  the  name  "  Heine-Medin  "  for  this  disease,  which 
was  so  kaleidoscopic  in  its  symptomatology,  so  variable  from  the 
point  of  view  of  pathological  evidence,  and  the  etiology  of  which 
was  so  entirely  unknown  at  that  time. 


OUR    KNOWLEDGE    OF    THE    NATURE    OF    THE    DISEASE  3 

No  one  can  object  to  the  association  of  the  names  of  these 
two  men  with  the  disease.  Heine  gave  the  first  classical  description 
of  the  disease,  and  Medin  was  the  first  to  correlate  the  various  types 
and  provide  us  with  a  comprehensive  view  of  the  disease.  It  is 
true  that  such  a  name  is  unsatisfactory  because,  where  possible, 
the  name  should  express  the  essential  character  of  any  disease;  but 
in  the  present  instance  our  knowledge  is  insufficient  to  enable  us 
to  do  this.  We  have  seen  what  difficulties  and  perplexities  stand 
in  the  way  of  any  anatomical  nomenclature,  and  it  must  be  admitted 
that  our  knowledge  of  the  question  of  etiology  is  still  in  its  infancy. 
The  wider  the  term  now  chosen,  the  less  will  be  the  likelihood 
that  future  researches  will  necessitate  further  change.  On  the 
other  hand,  there  is  no  fear  that  the  name  "  Heine-Medin  "  is  so 
wide  and  indeterminate  that  diseases  not  belonging  to  this  class 
will  be  included  under  it.  By  means  of  experiments  with  apes 
we  are  in  possession  of  an  infallible  criterion  to  decide  whether  a 
particular  doubtful  case  should  or  should  not  be  classified  as  one 
of  Heine-Medin  disease.  We  therefore  agree  with  Wickman  and 
in  future  shall  call  all  cases  belonging  to  the  group  which  he  has 
established  so  brilliantly,  both  from  its  clinical  as  well  as  from  its 
epidemiological  aspect,  cases  of  Heine-Medin  disease.  There  are 
further  practical  advantages.  During  the  epidemic,  in  answer  to 
my  question  as  to  whether  any  connection  could  be  traced  between 
a  particular  case  of  infantile  paralysis  and  previous  cases,  doctors 
have  frequently  replied  in  the  negative  because  they  have  known 
of  no  cases  of  paralysis.  If  the  name  "  Heine-Medin  "  be  adopted, 
it  is  to  be  hoped  that  the  discovery  of  Wickman  will  become  more 
widely  known,  namely,  that  although  paralysis  is  the  outstanding 
feature  of  the  disease  it  is  very  possibly  by  no  means  the  most 
common  feature. 

The  nomenclature  proposed  by  Wickman  will  be  used  in  this 
book;  at  the  same  time,  for  practical  reasons,  the  exciting  cause 
of  Heine-Medin  disease  will  be  referred  to  as  "  Poliomyelitis  Virus  " 
(abbreviated:  p.m.  virus).  This  term  expresses  one  of  the  most 
important  characteristics  of  the  virus,  which  has  not  been  isolated 
as  yet,  namely,  its  tendency  to  attack  the  grey  matter  of  the  spinal 
cord.  We  do  not  scruple  to  speak  of  the  virus  and  bacillus  A 
tuberculosis,  even  though  we  know  that  on  occasion  Koch's  bacillus 
does  not  form  tubercles. 

Historical  Retrospect. — As  in  most  directions  in  medicine,  we 
owe  our  knowledge  of  the  disease  of  Heine  and  Medin  to  a  few 
exceptional  men.  The  extent  of  our  indebtedness  to  them  will  be 
particularized  in  the  chapters  which  deal  separately  with  the  clinical 
aspect,  the  etiology,  the  epidemiology,  and  the  pathogenesis  of  the 
disease.  Others  have  done  much  in  a  small  way  to  fill  the  gaps 
left  by  the  men  of  wide  views  and  imagination,  but  as  time  pro- 
gresses their  work  will  become  more  and  more  of  an  anonymous 
character. 

At  the  beginning  of  the  history  of  the  disease  one  name  stands 


4  EPIDEMIC   INFANTILE   PARALYSIS 

out,  that  of  Jakob  v.  Heine.  It  is  to  his  credit  that  he  isolated  a 
type  of  flaccid  atrophic  paralysis  from  the  chaos  of  the  multitudinous 
forms  of  paralysis  affecting  children.  He  chose  the  name  "  Spinal 
Infantile  Paralysis  "  because  of  the  supposed  site  of  the  lesion. 
His  excellent  description  remained  for  years  the  basis  of  all  the 
accounts  of  the  disease  in  the  text-books,  and  for  a  long  time,  with 
the  exception  of  the  discovery  of  the  changes  in  the  electrical 
reactions  by  Duchenne  and  Erb,  no  important  addition  was  made 
to  it  by  other  observers.  It  was  not  until  the  occurrence  of  the 
great  Swedish  epidemics  that  Medin  and  Wickman  discovered  that 
the  disease  "  Spinal  Infantile  Paralysis  "  was  only  the  common 
symptom-complex  produced  by  a  disease  which  more  rarely 
appeared  in  a  bulbar,  cerebral,  polyneuritic,  ataxic,  meningitic  or 
abortive  form,  or  as  Landry's  paralysis.  Owing  to  the  length  of 
time  which  had  elapsed,  during  which  the  disease  had  been  con- 
sidered as  a  fully  described  entity,  the  many-sided  picture  of  the 
disease  drawn  by  the  Swedish  authors  was  surprising  and  noveL 
Many  considered  that  the  disease  so  described  had  nothing  to  do 
with  Heine's  disease,  while  others  fell  back  upon  the  hypothesis 
that  the  disease  had  changed  in  the  manner  of  its  manifestation. 
As  a  matter  of  fact,  the  only  change  which  had  taken  place  was 
in  the  extent  of  our  knowledge.  It  is  necessary  to  recognize  this- 
important  fact  in  estimating  the  value  of  the  contributions  of  the 
Swedish  investigators.  Their  results  have  been  confirmed  by  all 
the  painstaking  work  which  has  been  done  in  the  more  frequent 
epidemics  of  later  years. 

Pathological  and  anatomical  investigations  have  advanced  pari 
passu  with  the  clinical,  in  this  as  in  other  departments  of  medicine. 
Heine  placed  the  lesion  in  the  spinal  cord  on  theoretical  grounds; 
the  proof  of  the  existence  of  an  organic  lesion  was  furnished  later 
by  microscopical  investigation  at  the  hands  particularly  of  French 
authors  (Prevost  and  Vulpian,  Charcot  and  Joffroy,  Roger  and 
Damaschino).  who  called  attention  to  the  most  important  change  of 
all,  the  atrophy  of  the  ganglion  cells.  The  French  authors  also 
pointed  out  the  importance  of  the  interstitial  changes  which  occurred 
in  the  cord.  Subsequently,  pathological  discussion  raged  round  the 
question  whether  the  parts  primarily  affected  were  the  ganglion 
cells,  as  maintained  by  Charcot,  or  the  supporting  structures  of 
the  cord.  It  cannot  be  said  even  at  the  present  day  that  this 
question  has  been  decided  finally  one  way  or  another.  But  the 
researches  of  Rissler  in  acute  cases  have  enabled  us  to  say  definitely 
that  the  disease  consists  in  a  disseminated,  infiltrative,  inflamma- 
tory process,  which  may  attack  any  portion  of  the  central  nervous 
system,  but  which  shows  a  predilection  for  the  spinal  grey  matter. 
Wickman  particularly  not  only  confirmed  and  extended  our  know- 
ledge of  the  actual,  demonstrable,  pathological  changes,  but  threw 
new  light  upon  the  question  of  the  pathogenesis  of  the  disease. 
Recent  experiments  with  animals  appear  to  be  leading  to  a  still 
more  clear  conception  of  the  pathology  and  pathogenesis  of  Heine- 
Medin  disease. 


OUR    KNOWLEDGE    OF    THE    NATURE    OF    THE    DISEASE  5 

The  history  of  the  epidemiology  is  of  more  recent  date;  in 
the  'eighties  endemic  occurrence  of  the  disease  was  noted,  epidemics 
were  observed  only  at  the  beginning  of  the  'nineties.  The  first 
■epidemics  served  only  to  increase  clinical  knowledge  of  the  disease. 
Wickman 's  thorough  work  on  the  epidemiology  dates  from  1907; 
he  produced  proof  that  the  disease  is  contagious  and  his  conclusions 
have  been  borne  out  in  the  main  by  subsequent  investigators. 
Successful  investigation  of  the  etiology  is  of  very  recent  date. 
Since  Strumpell  first  came  to  the  conclusion  that  the  disease  was 
due  to  an  exogenous,  living  agent,  and  as  a  result  of  the  con- 
firmation of  his  views  by  subsequent  epidemics,  the  etiological 
aspect  has  had  similar  justification  and  importance  as  the  other 
.aspects  of  the  disease.  After  passing  through  several  phases  this 
work  has  now  entered  on  a  new  path  owing  to  the  success  of 
Landsteiner  in  transmitting"  the  disease  to  apes.  At  present  we 
are  at  the  beginning  of  this  line  of  research,  but  already  important 
additions  to  our  knowledge  of  the  active  agent  have  been  made, 
the  pathology  and  pathogenesis  becoming  better  known  thereby, 
while  at  the  same  time  a  further  stage  in  the  understanding  of  the 
■epidemiology  has  been  reached;  finally,  there  is  now  some  hope 
in  the  direction  of  actual  combating  of  the  disease,  either  by  means 
of  hygienic  measures  or  of  drugs. 

This  short  resume  of  the  history  of  the  disease  of  Heine  and 
Medin  bears  out  what  I  said  at  the  beginning,  that  it  resolves 
itself  into  a  series  of  steps  made  by  a  few  remarkable  men.  The 
clinical  aspect  is  bound  up  with  the  names  of  Heine,  Medin,  and 
Wickman;  pathological  research  from  the  purely  descriptive  point 
of  view  begins  with  Charcot's  teaching  that  the  ganglion  cells  are 
the  elements  primarily  affected,  and  the  critical  histological  studies 
of  Wickman  have  been  the  most  important  subsequent  additions 
to  our  knowledge  in  this  field.  Wickman  must  be  regarded  as  the 
founder  of  the  epidemiology,  while  Strumpell  laid  the  foundations 
of  the  etiology  of  the  disease  by  his  brilliant  hypothesis  and 
Landsteiner  has  led  the  way  in  the  elucidation  of  the  etiology  by 
means  of  his  experiments  on  animals. 


CHAPTER  II. 

The  Symptomatology  of  the  Disease  in  Man. 


I.— HISTORICAL. 

The  Period  before  Heine. — It  was  not  possible  that  such  a 
disease  could  have  been  overlooked  by  the  medical  profession  before 
Heine's  time.  The  credit  of  having  described  cases  is  generally 
given  to  the  Englishman,  Underwood,  who  flourished  about  the 
middle  of  the  eighteenth  century.  According  to  Seeligmuller's 
critical  analysis  of  the  report  it  appears  that  it  was  inaccurate  and 
did  not  differentiate  between  the  paralysis  due  to  spinal  infantile 
palsy  and  that  due  to  other  spinal  lesions,  e.g.,  vertebral  caries. 
The  German,  Jorg  (1816),  wrote  the  first  description  to  which 
exception  cannot  be  taken.     His  description  is  as   follows:  — 

The  little  girl  was  born  healthy,  although  the  mother  was  by  no 
means  strong.  When  a  few  weeks  old  the  child  suffered  from  some  violent 
fever,  of  the  nature  of  which  the  parents  could  tell  me  nothing,  but  which 
seemed  to  have  been  caused  by  a  chill  and  to  be  of  the  nature  of  those 
typhoid  fevers  to  which  children  are  so  subject  and  which  make  such 
devastating  inroads  on  their  whole  economy.  The  illness  lasted  a  long 
time,  and  the  parents  and  the  doctor  despaired  of  all  hope.  In  spite  of 
this  the  child  gradually  recovered  from  the  fever,  although  she  remained  for 
a  long  time  wasted  and  weak.  About  the  same  time  the  mother  suffered 
from  some  illness  of  which  she  very  nearly  died  and  the  child  consequently 
was  left  to  the  care  of  strangers.  When  the  mother  had  recovered  suffi- 
ciently to  resume  the  care  of  the  child  she  noticed  that  it  did  not  move 
its  feet  properly ;  it  became  more  and  more  clear  that  the  feet  were  becoming 
clubbed. 

Heine,  who  referred  to  this  case  of  Jorg,  also  called  attention 
to  an  observation  of  Briick  (1839),  who  mentions  the  case  of  a  boy 
who  developed  contractures  of  all  limbs  after  infantile  paralysis. 
The  case  reported  by  Badham  (1836),  quoted  in  full  by  Heine, 
probably  does  not  belong  to  this  group;  indeed,  the  author  himself 
regarded  the  paralysis  as  of  cerebral  origin.  The  communications 
of  Badham,  however,  are  of  importance  inasmuch  as  they  were 
the  cause  of  the  first  publications  of  Heine.  Badham  wrote  "  What 
is  the  cause  of  this  paralysis  ?     Of  what  nature  is  it  ?     What  is  to 


THE    SYMPTOMATOLOGY    OF   THE    DISEASE    IN    MAN  7 

be  done  against  it  ?  The  author  would  be  glad  to  know  the 
answers  to  these  questions  and  he  calls  upon  the  medical  men  of 
all  nations  to  publish  their  experiences  and  views  in  this  important 
matter.''  In  too  modest  a  fashion  Heine  prays  that  his  publication 
''  may  not  be  taken  to  be  an  answer  to  the  questions  put  before 
the  medical  world  by  the  English  doctor."  As  a  matter  of  fact, 
however,  Heine's  first  monograph  contains  as  complete  an  answer 
to  these  questions  as  was  possible,  considering  the  standpoint  of 
medicine  at  that  time  and  the  amount  of  material  which  was  at 
his  disposal. 

Heine's  Work. — The  method  of  Heine  throws  much  light  on 
the  methods  involved  in  all  successful  investigations.  It  follows 
in  the  main  a  procedure  opposite  to  that  used  by  Medin,  which 
we  shall  consider  later.  Heine  collected  cases  of  a  definite  type 
out  of  the  numerous  records  of  paralysis  in  children,  and  raised 
this  type,  the  flaccid  atrophic  spinal  type,  into  a  definite  clinical 
entity.  We  know  now  that  the  cases  selected  by  Heine  did  not 
exhaust  his  material  from  the  etiological  point  of  view,  and  that 
consequently  his  classification  was  too  narrow.  This  does  not 
detract  from  the  value  of  Heine's  services,  which  lay  in  the 
differentiation  of  a  type  from  amongst  the  medley  of  inco-ordinated 
observations  of  which  his  material  was  composed.  He  had  suc- 
ceeded in  discovering  the  most  common  form  of  the  disease  and 
his  work  is  a  standing  example  of  the  value  of  applying  an  arbitrary 
principle  in  a  schematic  and  orderly  way  to  a  mass  of  clinical 
observations;  the  result  may  not  give  a  complete  explanation  of 
all  the  appearances,  but  it  undoubtedly  leads  to  a  widening  of  our 
conception  of  the  disease  and  to  an  actual  increase  of  knowledge. 

In  the  text-books  and  in  many  modern  monographs  Heine  is 
given  credit  for  being  the  classical  observer  of  the  symptomatology 
of  the  chronic  stage  of  infantile  paralysis.  But  it  must  not  be 
forgotten  that  he  was  well  aware  of  the  acute  stage ;  he  writes : 
"  Two  stages  can  be  made  out  at  once,  a  primary  acute  stage 
and  a  secondary  chronic  one ;  the  two  stages  merge  into  one 
another  without  any  definite  dividing  line."  He  gives  the  following 
description  of  the  acute  stage :  — 

The  disease  attacks  children  who  are  healthy  and  well  developed  at 
the  age  of  from  6  to  36  months.  Usually  they  have  suffered  from  no  illness 
previously,  in  some  cases  they  have  been  somewhat  unwell  for  a  short  time. 
The  incidence  is  sudden,  occurring  with  fever,  congestion  of  the  head,  rest- 
lessness, and,  in  short,  symptoms  of  general  irritation.  At  the  same  time 
there  are  signs  of  difficulties  in  dentition,  the  children  put  their  hands  to 
their  mouths,  from  which  saliva  pours,  the  gums  are  swollen  in  places  and 
are  hot,  sleep  is  restless,  broken  by  paroxysmal  cries,  and  the  eyelids  are  only 
half  closed.  Sometimes  the  disease  begins  with  vomiting,  diarrhoea,  or  the 
appearances  of  acute  rheumatism.  Rarely  one  of  the  exanthemata  seems 
to  be  at  the  root  of  the  matter.  Subsequently  there  may  be  more  or  less 
severe  convulsions,  which  may  recur.  In  two  children,  whom  I  treated 
later,  the  illness  began  suddenly  with  convulsions,  collapse,  frothing  at  the 
mouth  and  nose,   and  lividity.     In  other  cases  the  paralysis  appears  after 


8  EPIDEMIC  INFANTILE  PARALYSIS 

only  slight  general  symptoms  of  fever  which  may  be  overlooked ;  the  child 
goes  to  bed  apparently  healthy  and  is  found  paralysed  in  the  morning. 
This  mild  type  of  onset  is  the  more  common  form  and  often  leads  both  the 
doctor  and  the  parents  to  take  too  hopeful  a  view  of  the  illness.  The  danger 
to  life  in  such  cases  is  very  slight,  but  there  is  no  doubt  that  in  the  more 
violent  cases  the  child  is  in  considerable  danger,  although  no  directly  fatal 
case  has  come  to  my  knowledge.  The  convulsions  are  limited  to  a  single 
attack  in  most  cases,  but  rarely  the  initial  attack  is  followed  by  several 
minor  paroxysms.  After  the  convulsions  the  child  lies  quiet,  pale  and 
exhausted,  looking  about  the  room  as  if  just  awakened  from  a  sleep — [in  the 
First  Edition  Heine  writes  "  paralysis  suspendit  convulsiones "]  and  it 
appears  to  the  parents  as  if  convalescence  will  be  rapid  until  they  find  on  lift- 
ing the  child  that  it  is  paralysed.  The  lower  extremities  are  most  frequently 
affected ;  often  in  conjunction  with  the  muscles  of  the  trunk,  so  that  the 
patient  not  only  loses  the  power  of  walking,  but  even  of  sitting  up  and 
of  holding  up  the  head.  Frequently  one  leg  is  affected,  but  without  the 
corresponding  arm,  as  in  the  hemiplegic  type  of  the  disease ;  a  few  separate 
muscles  may  be  affected  in  each  leg.  In  the  rarest  cases  one  arm  and 
shoulder  being  affected  the  limb  hangs  by  the  side,  while  the  lower 
extremities  remain  quite  untouched.  The  bladder  and  rectum  are  some- 
times weakened  for  a  time,  but  never  permanently  affected.  With  the 
occurrence  of  paralysis  the  first  stage  of  the  disease  is  finished  and  it  passes 
into  its  second  stage. 

This  description,  in  my  opinion,  is  still  worth  recalling  in 
the  light  of  our  subsequent  knowledge.  It  is  true  that  Heine 
depicts  the  acute  stage  mainly  from  facts  obtained  from  the  history 
of  the  cases,  but  this  scarcely  diminishes  the  value  of  his  state- 
ment, as  the  obtaining"  of  a  good  history  is  one  of  the  most 
important  parts  of  clinical  examination  and  is  an  art  in  itself  which 
is  by  no  means  understood  by  everybody.  Eduard  Miiller  has 
lately  called  attention  to  the  great  importance  of  a  good  history 
in  just  these  cases;  further,  the  doctor  rarely  has  an  opportunity 
of  observing  the  acute  stage  of  the  disease,  except  during  an 
epidemic.  Even  as  late  as  the  year  1878,  we  find  Seeligmuller  com- 
plaining that  there  was  but  one  description  of  the  acute  stage  in 
the  literature,  that  written  by  Dr.  Ehrenhaus,  an  assistant  of  Dr. 
Henoch. 

Heine  may  be  considered  the  founder  of  the  symptomatology 
of  both  the  acute  and  chronic  stages  of  the  disease.  Following 
on  a  short  communication  to  the  Society  for  the  Study  of  Natural 
History  at  Freiburg,  in  1838,  his  first  monograph  appeared  in 
1840.  In  this  he  describes  fourteen  cases  of  paraplegia,  seven  cases 
of  "  hemiplegia,"  which  term  he  uses  to  connote  paralysis  of  one 
extremity,  i.e.,  cases  which  we  should -call  monoplegia,  and  six 
cases  of  partial  paralysis.  In  the  same  monograph  he  describes 
four  cases  of  paralysis  due  to  cerebral  lesion,  which  he  differentiates 
sharply  from  the  rest  by  laying  stress  on  the  spastic  nature  of  the 
paralysis ;  he  thus  lays  the  foundation  of  his  classification  of  the 
paralyses  according  to  their  spastic  or  non-spastic  character,  which 
classification  has  been  adhered  to  down  to  the  present  day.     The 


THE    SYMPTOMATOLOGY    OF   THE    DISEASE    IN    MAX  CJ 

correctness  and  comparative  completeness  of  his  description  is 
generally  admitted;  in  particular  he  called  attention  to  the  absence 
of  sensory  disturbance  and  to  the  fact  of  recovery  taking"  place 
from  even  extensive  paralysis.  He  says  also :  :<  The  gradual 
reduction  of  the  paralysis,  both  in  extent  and  in  intensity,  gives 
ground  for  the  belief  that  it  is  due  to  the  gradual  re-absorption 
of  exudate  around  the  nervous  elements,  -  whereby  the  latter  are 
partially  relieved  from  pressure."  This  shows  that  he  had  some 
idea  of  the  nature  of  the  pathological  process  involved.  He 
recognized  that  the  mental  condition  of  his  patients  was  good 
("  some  of  them  showed  much  talent "),  and  he  describes  with 
great  clearness  the  paralysis,  the  atrophy,  the  contractures,  the 
delayed  growth  of  bone  and  the  other  deformities.  From  the  point 
of  view  of  etiology,  he  believes  that  delayed  and  difficult  dentition 
is  to  be  blamed.  Finally,  he  showed  the  way  towards  the  correct 
orthopaedic  treatment  of  the  permanently  paralysed. 

It  is  surely  of  value  to  save  from  oblivion  the  life-history  of  so  remark- 
able a  man.  Bv  the  courtesy  of  Dr.  Sick,  the  Director  of  the  Municipal 
Hospital  of  Stuttgart,  I  am  in  possession  of  the  Proceedings  of  the  Wiirlem- 
berg  Medical  Society;  in  vol.  1,  188.0,  there  are  to  be  found  the  following 
biographical  notes  : — ■ 

"  Jakob  Heine  was  born  April  16,  1800,  at  Lauterbach,  a  village 
in  the  Black  Forest.  His  father  kept  an  inn,  and  was  also  a  farmer. 
At  first  he  attended  the  village  school,  but  he  soon  showed  desire 
for  a  wider  education.  When  aged  13  he  tried  to  enter  the  Gymnasium  at 
Rottweil,  but  was  not  accepted  as  he  was  already  too  old.  For  some  time 
he  followed  his  father's  occupation.  The  desire  for  a  scientific  training 
left  him  no  peace,  and  at  the  age  of  21  he  entered  the  classical  school 
at  Altirsbach,  where  he  worked  side  by  side  with  boys  from  8  to  14  years 
old.  In  the  autumn  of  1822  he  entered  the  Gymnasium  at  Rottweil,  and  in 
a  short  time,  by  untiring  effort,  he  passed  his  examination.  In  1S23  he 
entered  the  University  of  AVtirzburg,  where  the  influence  of  his  uncle  Heine, 
'  the  Father  of  Orthopaedics,-'  soon  caused  him  to  give  up  theology  for 
medicine.  He  carried  on  his  studies  with  great  assiduity  and  under  many 
difficulties.  He  acted  for  a  time  as  assistant  to  Schonlein,  and  in  the 
surgical  clinic  of  Textor ;  he  was  also  prosector  of  anatomy.  He  graduated 
in  AVtirzburg,  and  passed  the  AViirtemberg  State  Examination  at  Tubingen 
in  1S29.  Shortly  afterwards  he  was  asked  to  arrange  a  State  orthopaedic 
hospital.  He  chose  the  town  of  Cannstadt,  where  he  opened  the  institution 
in  1829.  As  so  often  happens  when  a  new  special  hospital  is  founded,  the 
patients  who  appeared  wanting  orthopaedic  treatment  seemed  literally  to 
spring  out  of  the  ground,  and  enlargement  of  the  hospital  speedily  became 
necessary.  Heine  married  Henriette  Camerer,  daughter  of  the  Director  of 
the  Catholic  Council  in  Stuttgart,  in  1831.  Patients  of  all  countries  and 
of  all  ranks  came  in  great  numbers  to  his  institution. 

"  Apart  from  the  two  monographs  which  appeared  in  1840  and  i860 
Heine  did  not  write  anything. 

"  He  received  many  personal  honours.  In  1830,  as  a  result  of  the 
immediate  success  of  his  institution,  he  was  given  the  freedom  of  the  town 
of  Cannstadt  and  the  title  Hofrat.  Later  he  obtained  the  title  Geheimer 
Hofrat,  and  was  the  recipient  of  many  Orders.     He  retired  into  private  life 


IO  EPIDEMIC   INFANTILE  PARALYSIS 

in  1S65.  He  had  the  proud  pleasure  of  seeing  one  of  his  sons  become 
surgeon  and  lecturer  at  the  University  of  Prague,  although  he  had  the 
sorrow  of  seeing  this  same  son  die  before  him  in  1S77.  Heine  died 
November  12,  1879,  in  Cannstadt.  His  life  was  that  of  a  man  of  manly 
character  who  rejoiced  in  overcoming  obstacles;  he  is  said  to  have  'had 
good  luck,'  but,  as  a  matter  of  fact,  his  success  was  due  to  his  magnificent 
energy  and  self-confidence. "; 

The  best  clinicians,  Romberg,  Bardeleben,  Duchenne,  and 
Rilliet  praised  his  work.  Rilliet  and  Barthez,  who  wrote  on 
infantile  spinal  paralysis  in  1843,  did  not  know  of  his  work  at  that 
time  and  used  the  term  '*  essential  infantile  paralysis  "  because 
they  were  unable  to  find  any  changes  in  the  spinal  cord  post 
mortem.  In  a  later  work  (.1851)  they  recognized  the  importance 
of  Heine's  work,  but  again  rejected  the  term  "spinal,"  owing  to 
their  repeated  negative  results  at  autopsies. 

In  England  attention  was  turned  to  the  paralyses  of  children. 
In  1850,  Kennedy  described  cases  of  "temporary  paralysis"  in 
which,  however,  there  is  some  doubt  as  to  whether  they  were  due 
to  the  same  cause  as  Heine's  cases.  The  English  physician,  West, 
coined  the  term  "paralysis  of  the  morning"  in  1852;  this  term 
was  used  for  a  long  time,  although,  judged  by  the  standard  of  our 
present  knowledge,  it  has  little  to  recommend  it.  In  i860,  Heine's 
second  monograph  appeared;  in  it  he  gives  records  of  150  further 
cases,  and  localizes  the  lesion  in  the  spinal  cord  with  certainty  by 
purely  deductive  reasoning.     We  shall  return  to  this  point  later. 

From  Heine  to  Medin. — The  next  thirty  years  did  not  add 
much  to  the  clinical  knowledge  of  the  disease.  Of  importance  was 
the  demonstration  of  the  change  in  the  faradic  reactions  of  the 
muscles  by  Duchenne,  and  his  conclusion  from  this  that  the  disease 
was  spinal  in  its  localization.  He  invented  the  name  "  Paralysie 
atrophique  graisseuse  de  l'enfance,"  which  was  but  little  used. 
Erb  followed  with  observations  on  the  changes  in  the  galvanic 
reactions  and  formulated  his  theory  of  the  "  reaction  of  degenera- 
tion." Otherwise,  as  far  as  progress  in  the  field  of  clinical  in- 
vestigation was  concerned,  the  period  produced  nothing.  The 
text-books  of  the  time  followed  Heine's  description,  with  the 
addition  of  the  results  of  investigations  of  Duchenne  and  Erb. 
Many  isolated  observations  were  put  on  record  during  the  years 
i860  to  1890,  which  tended  more  and  more  to  show  that  the 
description  given  by  Heine  was  becoming  too  narrow  and  that 
the  conception  of  the  disease  needed  broadening'.  However, 
nothing  definite  was  achieved,  firstly,  because  the  several  observa- 
tions remained  isolated,  and.  secondly,  because  at  that  time  men's 
energies  were  directed  mainly  in  the  direction  of  topographical 
diagnosis.     The  man  with  true  scientific  insight  had  not  arrived. 

Among  these  observations,  which  showed  that  the  limit  drawn 
by  Heine  was  too  narrow,  were  some  which  proved  that  the  disease 
might  attack  adults.  Such  were  those  of  Meyer  (i860),  Duchenne 
fils  (1864),  and  particularly  the  elder  Duchenne,  Erb  and  Charcot, 


THE     SYMPTOMATOLOGY     OF     THE     DISEASE     IN     MAN  II 

who  based  their  conclusions  on  positive  anatomical  evidence. 
Others  were  Schultze,  1878;' Friedlander,  1882;  Leri  and  Wilson, 
Rissler,  1888;  Leegaard,  1889;  Williamson,  v.  Kahlden,  Middleton, 
Jagic,  Roder  and  Bickel,  Sherman  and  Spiller,  Taylor,  van 
Gehuchten. 

Some  observers  pointed  out  the  similarity  or  even  the  identity 
of  the  pathological  processes  in  infantile  paralysis  and  Landry's 
disease.  These  were  Petit  fils,  Zimmermann,  who  in  1885  examined 
a  case  of  Landry's  paralysis  and  came  to  the  conclusion  that  this 
disease  and  infantile  paralysis  formed  only  different  degrees  of  one 
and  the  same  disease;   Buss  in   1887,  and  particularly  Raymond. 

In  other  directions  also  the  accepted  idea  of  the  disease  began 
to  fall  in  pieces.  Erb  recognized  that  there  are  cases  of  paralysis 
which  are  identical  with  infantile  paralysis  and  which  end  in  com- 
plete recovery;  Duchenne  in  1855,  Volkmann  in  1870,  and  Frey 
in  1874,  had  already  described  similar  cases.  The  similarity  be- 
tween certain  forms  of  paralysis  due  to  medullary  and  pontine 
lesions  and  anterior  poliomyelitis  was  put  on  record.  Eisenlohr, 
in  1880,  described  some  typical  cases.  But  it  was  Oppenheim  who 
in  1883  formulated  clearly  an  "  encephalitis  pontinea,"  which  was 
in  close  relationship  to  infantile  paralysis.  Thus  we  see  how  the 
original  conception  of  the  disease  gradually  became  widened;  but, 
owing  to  the  absence  of  any  criterion  by  which  the  several  varieties 
could  be  judged  and  included  or  excluded  in  the  general  group, 
no  definite  restatement  of  the  position  was  possible. 

The  most  important  advance  was  made  by  Strumpell;  he  placed 
certain  cerebral  palsies  in  the  same  group  with  the  spinal  infantile 
palsies.  The  importance  of  this  step  lies  in  the  appearance  of  a 
new  etiological  standpoint,  by  which  Strumpell  justified  his  classifi- 
cation, and  which  was  accepted  later  by  Jendrassik  and  Fierre 
Marie.  Strumpell  also  connected  etiologically  certain  forms  of 
neuritis  with  poliomyelitis.  I  have  no  doubt  that  if  Strumpell 
had  had  the  opportunity  of  observing  an  epidemic  he  would  have 
antedated  the  discoveries  made  by  Medin.  His  arguments  seem  to 
me  to  be  of  such  importance  as  to  merit  quotation.  In  1884  he 
wrote  :  — 

Even  the  general  course  of  these  diseases  shows  great  similarity. 
Multiple  neuritis  and  poliomyelitis  appear  in  similar  varieties ;  they  show 
the  same  gradation  between  the  acute  and  the  chronic  forms.  Both  affect 
principally  the  motor  tracts,  although  owing  to  the  peripheral  nerves  being 
affected  in  the  one  and  the  spinal  cord  in  the  other  there  are  many  minor 
differences  in  the  symptoms.  It  follows  that  the  purely  anatomical  classi- 
fication between  neuritis,  poliomyelitis,  and  acute  encephalitis,  which  is 
now  in  vogue  must  be  looked  upon  as  an  artificial  one.  It  seems  to  us 
worth  while  to  consider  whether  all  these  diseases  may  not  be  brought  under 
one  etiological  heading,  and  whether  they  may  not  be  considered  to  be 
different  local  manifestations  of  the  same  disease,  or  at  least  of  very  closely 
allied  diseases.  In  this  connection  one  might  apply  the  analogy  between 
croup     and     faucial     diphtheria     to     the     diseases,    multiple    neuritis     and 


12  EPIDEMIC  INFANTILE  PARALYSIS 

poliomyelitis.  It  is  only  of  late  years  that  the  former  diseases  have  been 
recognized  as  arising  from  the  same  cause,  whereas  for  many  years  a  purely 
artificial  distinction  was  made  between  them. 

In  the  year  1885  he  writes  :  — 

Both  diseases  tend  to  attack  previously  healthy  children  in  infancy. 
They  present  a  stage  of  acute  invasion  in  which  they  can  scarcely  be 
differentiated;  this  leaves  a  paralysis  behind  it  which  in  both  diseases 
affects  the  motor  tracts,  in  the  case  of  poliomyelitis  the  grey  matter  of  the 
cord,  in  the  case  of  the  hemiplegic  palsies  undoubtedly  the  brain ;  this 
resultant  palsy  is  naturally  of  different  kinds,  but  the  differences  are  due 
merely  to  the  localization  of  the  disease  and  not  to  any  difference  of  the 
essential  nature  of  it.  In  any  case  the  analogy  between  the  two  diseases 
is  remarkable  in  that  in  both  cases  it  is  the  grey  matter  which  is  affected. 
That  in  the  hemiplegic  cases  the  cortex  of  the  brain  is  affected  is  proved 
by  the  distribution  of  the  paralysis,  the  occurrence  of  epileptic  attacks  and 
athetosis  afterwards,  and,  from  the  anatomical  aspect,  by  the  results  of 
microscopical  examination.  In  these  cases  porencephaly  is  found  which  is 
not  of  the  kind  present  in  cases  of  congenital  defect,  but  which  still  shows 
evidences  of  its  inflammatory  origin;  further,  this  porencephaly  is  found 
in  the  central  convolutions,  that  is  to  say,  in  the  motor  regions.  The 
appearances  are  precisely  similar  to  those  found  in  the  anterior  horns  after 
an  attack  of  poliomyelitis.  There  is  at  present  no  record  of  pathological 
investigation  of  the  acute  stage  of  either  disease. 

It  seems  to  me  to  be  justifiable  to  class  acute  encephalitis  as  a  by  no 
means  rare  variety  of  acute  anterior  poliomyelitis.  Personally,  I  lean 
towards  the  opinion  that  the  two  diseases  are  of  the  same  essential  type, 
or  are  even  identical,  inasmuch  as  both  are  due  to  the  same  agent,  possibly 
of  an  infective  nature,  which  attacks  sometimes  the  grey  matter  of  the  cord 
and  at  others  the  cerebral  cortex.  In  order  to  express  this  relationship  in 
the  nomenclature,  I  should  recommend  that  this  particular  form  of  hemi- 
plegia should  be  called  cerebral  infantile  paralysis  or  polioencephalitis 
acuta  in  contradistinction  to  spinal  infantile  paralysis  or  poliomyelitis 
acuta.  The  diagnosis  of  the  former  is  arrived  at  easily  by  means  of  careful 
investigation ;  at  the  same  time  the  existence  of  hemiplegia  in  children 
due  to  other  causes  must  not  be  lost  sight  of. 

These  different  observations  prepared  the  way  for  Medin.  The 
first  great  Swedish  epidemic  enabled  him  to  place  on  a  firm  basis 
the  relationship  between  the  various  types  of  this  disease,  which 
until  then  had  been  classed  as  strictly  separate  entities.  He 
observed  not  only  the  classical  spinal  form  as  well  as  the  cerebral 
and  the  polyneuritic  forms  (thereby  confirming  the  brilliant  theory 
of  Strumpell),  but  also  the  bulbar  form  and  cases  of  a  peculiar 
ataxia.  All  these  could  be  traced  as  occurring"  in  considerable 
numbers  within  the  same  epidemic,  and  so  were  doubtless  due  to 
the  same  cause.  Heine's  classical  description  of  the  simple  spinal 
form  was  thus  amplified;  the  disease  appeared  to  be  one  attacking 
the  whole  nervous  system  in  a  patchy,  disseminated  manner,  and 
producing,  according  to  its  particular  localization,  a  kaleidoscopic 
variety  of  clinical  pictures.  At  the  Berlin  Congress,  where  Medin 
published  his  results,  Heubner  recognized  at  once  their  fundamental 


THE    SYMPTOMATOLOGY    OF   THE    DISEASE    IN    MAN  1 3 

importance.  Medin,  the  first  to  have  the  opportunity  of  observing 
the  acute  stage  of  the  disease,  thus  became  the  founder  of  the 
symptomatology  of  this  stage. 

Medin  to  Wickman. — In  the  following-  years  there  occurred 
several  smaller  epidemics  which  enabled  Medin's  observations  to 
be  confirmed.  Hoffmann,  in  1894,  observed  a  brother  and  sister, 
the  one  suffering  from  the  spinal,  the  other  from  the  cerebral  form. 
Calabrese  also  identified  the  cerebral  and  spinal  types.  Zappert 
observed  the  Austrian  epidemic  of  1898  and  found  an  increasing- 
number  of  cerebral  cases. 

Besides  many  confirmatory  observations,  there  were  many 
which  opened  up  new  ground.  Duquennoy  (1898)  noted  a  particu- 
larly painful  type.  Schultze,  Auerbach,  also  Caverley  and  Macphail 
in  an  epidemic,  noted  the  frequent  involvement  of  the  meninges; 
unfortunately,  these  observers  fell  into  the  error  of  confounding 
the  disease  with  cerebro-spinal  meningitis. 

The  clinical  studies  of  \\  lckman  form  the  completion  of  this 
period.  By  his  wonderful  histological  work  he  made  important 
additions  to  our  knowledge  and  he  described  a  meningitic  form, 
also  a  type  simulating  Landry's  disease  and  particularly  an  abortive 
form  of  the  disease.  His  work  was  fully  corroborated  during  the 
epidemics  of  1908  and  1909  by  Leegaard  in  Norway  and  by  Zappert 
in  Austria;  Eduard  Miiller  made  an  exhaustive  clinical  study  of 
the  epidemic  in  Hesse. 

The  names  Heine,  Medin,  and  Wickman  mark  the  commence- 
ment of  three  important  periods  in  the  history  of  our  knowledge 
of  this  disease. 

II.— THE  SYMPTOMATOLOGY  IN  MAN. 

I  have  neither  the  intention  nor  the  capacity  to  give  a  complete 
description  of  the  symptomatology.  I  intend  to  give  merely  a 
short  sketch  of  the  subject  as  worked  out  by  Wickman  and  Eduard 
Muller.  in  order  that  the  reader  may  be  in  a  position  to  institute 
direct  comparisons  with  the  clinical  picture  seen  in  the  case  of 
apes,  which  I  shall  describe  later.  For  more  complete  information 
I  refer  the  reader  to  the  monographs  written  by  Wickman  and 
Eduard  Muller. 

Period  Of  Incubation. — This  lasts  at  least  five  days;  it  is 
usually  not  more  than  ten  days,  and  its  average  duration  is  about 
a  week.  Wrickman  suggests  the  possibility  that  it  may  last  only 
one  day,  but  his  conclusion  rests  upon  an  inadequate  interpretation 
of  certain  epidemiological  observations.  I  may  mention  here  that 
the  incubation  period  in  apes  may  be  much  longer  and  that  this 
may  be  the  case  also  in  man. 

Prodromal  Symptoms. — The  disease  does  occur  suddenly  with- 
out any  prodromal  symptoms  (the  "  paralysis  of  the  morning  "), 
but  this  is  exceedingly  rare;  usually,  there  are  symptoms  for  a 
variable   length   of  time,    one   to   seven   days.     The   most   common 


14  EPIDEMIC    INFANTILE  PARALYSIS 

is  fever  of  no  great  degree,  which  is  sometimes  remittent,  some- 
times continuous.  The  degree  of  fever  and  the  severity  of  the 
prodromal  symptoms  generally  bear  no  relation  to  the  amount 
of  subsequent  paralysis.  The  frequency  of  the  pulse  is  increased, 
and  more  than  proportionately  to  the  temperature;  Eduard  Miiller 
suggests  that  this  may  be  due  to  implication  of  the  bulbar  centres. 
Finally,  there  is  general  malaise.  Occasionally  a  rash  is  seen,  very 
rarely  herpes  labialis  (an  important  differential  point  with  regard 
to  cerebro-spinal  meningitis)  and  herpes  zoster.  Some  authors 
are  inclined  to  include  herpes  zoster  as  one  type  of  the  disease; 
we  shall  return  to  this  point  later. 

Quite  frequently  the  respiratory  tract  is  affected;  the  patient 
suffers  from  coryza  with  conjunctivitis,  from  bronchitis  or  even 
from  broncho-pneumonia.  In  some  epidemics,  e.g.,  in  our  Hessian 
one,  the  respiratory  tract  is  much  more  frequently  involved  than 
the  alimentary  tract,  which  in  other  epidemics  is  a  favourite  seat 
of  the  initial  symptoms;  vomiting,  diarrhoea  or  constipation  may 
occur.  Examination  of  the  blood  shows  leucopenia  (Eduard 
Miiller),  which  is  of  much  diagnostic  value  in  certain  cases. 

The  most  important'  prodromal  symptoms  are  those  connected 
with  the  nervous  system.  \\ "ithout  any  definite  psychical  disturb- 
ance there  is  a  certain  degree  of  somnolence:  rarely  convulsions 
and  tremors  occur  (they  are  noted  more  frequently  by  the  older 
writers):  of  particular  importance  is  a  general  tenderness  of  the 
whole  person:  this  is  characteristic  and  was  observed  by  Heine, 
Duchenne,  and  others.  Even  a  light  touch  causes  pain  which  is 
increased  by  passive  movement,  particularly  if  the  spine  be  involved 
in  the  movement.  Spontaneous  pain  occurs  in  the  limbs  and  in 
the  neck  and  back;  the  spine  feels  stiff.  There  may  be  some 
tenderness  to  pressure  of  the  nerve  trunks.  The  cause  of  most 
of  the  sensory  symptoms  lies  in  the  involvement  of  the  pia  mater. 
Excessive  sweating  is  a  characteristic  and  has  been  observed  by 
many  authors;  Miiller  has  found  it  in  three-quarters  of  his  cases; 
it  may  be  due  to  invoh'ement  of  the  spinal  sweat  centres,  which 
are  said  to  exist  in  the  anterior  horns  of  the  grey  matter. 

It  may  be  said  that  the  initial  symptoms  present  no  definite 
diagnostic  picture;  according  to  the  predominance  of  any  one  group 
of  symptoms,  the  appearances  may  be  meningeal,  gastro-intestinal. 
respiratory,   or  merely  generally  febrile  in  type. 

Stage  of  Paralysis. — This  stage  is  characterized  by  an  extra- 
ordinary variety  of  symptoms.  The  following  classification  of 
types,  as  proposed  by  Wickman.  cannot  be  made  to  fit  every  case. 
because  so  many  are  intermediate  between  two  types.  It  has  been 
suggested  that  Wickman' s  classification  should  be  simplified,  but 
I  cannot  see  any  good  reason  why  this  should  be  done. 

(a)  Abortive  Type. — Some  of  the  earlier  authors,  Briegleb. 
Pasteur,  Aledin.  and  Leegaard.  observed  cases  of  general  fever 
which  were  in  close  contact  with  cases  of  definite  infantile  paralysis; 
but    it    was    Wickman    who    first    clearly    proved    the    connection 


THE    SYMPTOMATOLOGY    OF   THE    DISEASE    IN    MAX  15 

between  the  two  groups  of  eases  and  brought  into  prominence  the 
abortive  type  of  the  disease.  This  type  consists  essentially  of  the 
prodromal  symptoms,  which  clear  up  without  any  paralysis.  Cases 
do  occur  which  lie  between  the  true  abortive  and  the  spinal  type; 
in  these  there  may  be  a  slight  temporary  weakness  of  one  muscle 
or  group  of  muscles,  or  there  may  be  merely  a  temporary  loss 
of  a  deep  reflex — the  "  rudimentary  poliomyelitis  "  of  Eduard 
Miiller. 

The  proportion  of  abortive  to  paralytic  cases  varies  in  different 
epidemics  and  in  the  several  foci  of  the  same  epidemic.  Wickman 
himself  has  recorded  figures  varying  from  35  per  cent,  to  56  per 
cent.  Miiller  believes  that  about  50  per  cent,  of  all  cases  are 
abortive.  The  etiological  identity  of  the  abortive  and  paralytic 
cases  is  proved  by  the  simultaneous  occurrence  of  both  types 
in  the  same  family,  and  latterly  by  the  serum  test  (vide 
Chapter  VI). 

(b)  Spinal  Types. — These,  forming  the  classical  spinal  infantile 
paralysis,  together  with  the  abortive  type,  make  up  the  great  bulk 
of  the  cases.  They  are  characterized  by  the  occurrence  of  paralysis 
either  during  or  subsequent  to  the  febrile  attack.  At  first  there  is 
only  paresis,  but  this  quickly  develops  into  paralysis.  The  extent 
of  the  paralysis,  the  muscle  groups  involved,  and  the  degree  of 
loss  of  function,  all  vary  within  very  wide  limits.  Most  frequently 
the  lower  limbs  are  attacked,  particularly  the  peronei  and  the 
quadriceps,  next  often  the  shoulder  muscles.  The  muscles  of  the 
buttocks,  which  are  involved  in  two-thirds  of  the  cases,  according 
to  Eduard  Miiller,  and  the  abdominal  muscles  are  often  affected 
but  frequently  overlooked.  Xot  infrequently  the  intercostals  are 
attacked,  the  diaphragm  more  rarely,  and  the  muscles  of  the  back 
and  neck  least  of  all.  In  short,  any  and  every  muscle  may  be 
affected,  but  those  of  the  lower  extremities  most  frequently  of  all. 
The  paralysis  is  of  the  flaccid  type,  the  tone  of  the  muscles  being 
diminished;  the  deep  reflexes  are  depressed  or  abolished;  the 
electrical  reactions  show  quantitative  diminution  of  excitability  and 
a  partial  or  complete  reaction  of  degeneration;  muscular  atrophy 
follows  on  the  paralysis.  At  the  commencement  of  the  illness  there 
may  be  an  increase  in  the  deep  reflexes;  Forster  has  even  recorded 
the  occurrence  of  ankle  clonus.  Midler  considers  that  involvement 
of  the  pyramidal  tracts  is  indicated  hereby.  The  fact  that  flaccid 
paralysis  does  not  occur  is  therefore  of  no  diagnostic  significance 
in  excluding  Heine-Medin  disease.  The  degree  of  paralysis  may 
vary  from  the  mere  loss  of  a  deep  reflex  to  the  most  complete 
flaccid  paralysis. 

Disturbances  of  micturition  are  rare  during  the  paralytic  stage, 
bur  a  form  of  retention  which  is  undoubtedly  nervous  in  origin  is 
frequent  in  the  acute  stage  (Miiller).  Incontinence  of  either  urine 
or  fseces  is  exceedingly  rare. 

The  essential  characteristic  of  the  disease  is  therefore  a 
motor   paralysis.     Disturbance    of   sensation   is    of   relatively   small 


i6 


EPIDEMIC   INFANTILE   PARALYSIS 


importance.  Loss  of  sensation  to  a  greater  or  less  degree  has  been 
observed,  and  Miiller  lays  stress  on  relative  thermanssthesia  and 
analgesia  occurring'  frequently,  if  only  transitorily,  at  the  beginning 
of  the  disease;  this  may  be  due  to  some  involvement  of  the  posterior 
horns. 

The  stage  of  repair  follows  that  of  acute  paralysis,  and  after 
about  one  to  one  and  a  half  years  the  chronic  stage  begins.     After 


Fig.  i. 

The  spinal  form  of  Heine-Medin  disease  with  paralysis  and  atrophy  of 
the  left  upper  extremity  dating  from  infancy.  The  muscles  of  the  shoulder- 
girdle  are  most  affected.      (After  Byrom  Bramwell.) 


this  no  further  recovery  of  power  is  to  be  expected,  and  in  young, 
growing  individuals  it  is  during  this  stage  that  deformities  appear. 
There  are  also  vasomotor  disturbances,  the  limbs  are  cyanosed  and 
cold  and  the  muscular  atrophy  becomes  marked  (fig.  i). 

The  most  common  deformities  are  pes  cavus  and  in  children 
scoliosis  (figs.  2  and  3). 


THE    SYMPTOMATOLOGY    OF   THE    DISEASE    IN    MAN 


17 


Occasionally  there  is  a  recurrence  of  the  disease  occurring-  at 
an  interval  of  some  weeks  or  even  months  after  the  first  attack 
(Medin,  Leegaard,  Neurath,  Schwarz).  But  Miiller  has  pointed 
out  that  every  increase  of  paralysis  occurring  after  an  interval  is 
not  to  be  regarded  as  a  recurrence  of  the  primary  disease,  but  is 
often  due  to  tracts  or  centres  which  were  damaged  suddenly 
refusing  to  work. 

(c)  A  Type  which  simulates  Landry's  Disease. — I  have  already 
mentioned  certain  isolated  records  of  cases  which  point  to  the 
identity  of  Heine-Medin  disease  and  Landry's  disease.  In  the 
year  1859,   Landry  described  a  disease  which  began  as  a  paralysis 


Fig 


Fig 


The    spinal    form   of    Heine-Medin    disease    with    extensive    paralysis    and 
deformity.      (After  Johannessen.) 


of  the  limbs  and  rapidly  progressed  to  a  fatal  issue  by  involving 
the  medullary  centres.  The  history  of  this  disease  furnishes  a 
good  example  of  the  way  in  which  an  arbitrary  and  narrow 
classification  may  prevent  the  recognition  of  wide  and  important 
relationships  between  diseases.  Observers  overlooked  the  fact, 
which  was  clear  from  the  identity  of  the  anatomical  findings,  that 
Landry's  paralysis  was  only  "  infantile  paralysis  "  with  a  fatal  issue; 
further,  that  fatal  cases  of  infantile  paralysis  ran  the  same  clinical 
course  as  cases  of  Landry's  paralysis.  As  Wickman  said,  they 
2 


l8  EPIDEMIC   INFANTILE  PARALYSIS 

appear  to  have  made  the  death  of  the  patient  the  essential  feature 
of  the  diagnosis.  During  the  Swedish  epidemic,  Wickman  was 
able  to  convert  the  probability  of  the  identity  of  the  two  diseases 
into  a  certainty.  The  basis  of  this  type  is  a  "  poliomyelitis 
acutissima,"  beginning  in  the  centres  for  the  lower  limbs,  spread- 
ing rapidly  to  those  for  the  upper  limbs  and  leading"  to  a  fatal 
issue  in  a  few  days  by  involving  the  centres  in  the  medulla.  In 
a  few  cases  the  arms  are  affected  first,  the  paralysis  being  simul- 
taneously ascending  and   descending. 

(d)  Bulbar  and  Pontine  Types. — Medin  was  the  first  to  call 
attention  to  the  frequency  with  which  the  cranial  nerves  were 
attacked.  It  is  rare  to  see  them  involved  alone;  usually  the  spinal 
centres  are  affected  at  the  same  time.  The  facial  nerve  is  the  one 
most  frequently  paralysed,  generally  on  one  side  only  and  in  its 
whole  distribution.  With  it  is  associated  sometimes  the  hypo- 
glossal (figs.  4  and  5). 


Fig  4.  Fig.  5. 

The  bulbar  form  of  Heine-Medin  disease  with  paralysis  of  the  left  facial 
and  hypoglossal  nerves.  In  fig.  5  the  patient  is  trying  to  close  both  eyes. 
(After  Wickman.) 


More  rarely  the  abducens  and  the  motor  oculi  are  involved, 
and  occasionally  the  trochlear  nerve.  Nystagmus  has  been 
observed  by  Medin,  Miiller,  and  Netter.  The  optic  nerve  has  been 
affected;  the  trigeminal,  as  shown  by  paralysis  of  movements  of 
the  lower  jaw,  and  very  rarely  the  other  cranial  nerves.  The 
clinical  picture  is  extraordinarily  variable,  according  to  the  particular 
nerves  affected,  the  degree  of  their  paralysis  and  the  amount  of 
involvement  of  the  spinal  cord  which  is  present.  Of  course,  all 
isolated  palsies  of  cranial  nerves  are  not  due  to  Heine-Medin 
disease  and  in  such  cases  serum  diagnosis  is  of  great  importance 
(vide  Chapter  VI). 

(e)  Cerebral  Type. — Striimpell  maintained  the  identity  of  cer- 
tain   encephalitic    processes    with    epidemic     poliomyelitis.      Medin 


THE    SYMPTOMATOLOGY    OF   THE   DISEASE    IN    MAN  19 

confirmed  his  views,  but  they  were  not  generally  accepted  owing 
to  the  rarity  of  observations  on  cerebral  cases.  At  the  present 
time  there  can  be  no  doubt  of  the  existence  of  such  cases.  Patho- 
logical encephalitic  lesions  quite  analogous  to  those  found  in  the 
spinal  cord  have  been  seen,  and  during  epidemics  spastic  and  flaccid 
cases  have  been  observed  side  by  side  by  Mobius,  Medin,  Buccelli, 
Hoffmann,  Leegaard,  Eduard  Miiller,  Zappert,  Spieler,  Schlesinger, 
Nonne,  and  Krause;  they  have  been  observed  in  the  same  patient 
by  Williamson.  Neurath,  Calabrese,  Oppenheim,  Pierre  Marie, 
and  Wickman.  The  serum  diagnosis  is  of  value  both  in 
proving  the  existence  of  encephalitis  due  to  Heine-Medin  disease 
as  also  in  differentiating  that  from  encephalitis  due  to  other 
causes. 

{f)  Ataxic  Type. — Medin  first  described  ataxia  similar  to  that 
seen  in  Friedreich's  disease,  also  Wickman,  Zappert,  Spieler, 
Lindner  and  Mally,  Netter,  Nonne,  and  others.  Zappert  does  not 
consider  it  advisable  to  make  a  special  ataxic  group;  he  prefers  to 
classify  such  cases  in  the  pontine  group.  Wickman,  on  the  other 
hand,  holds  that  all  the  ataxic  cases  are  not  due  to  a  lesion  in  the 
pons  or  medulla,  but  that  some  are  caused  by  lesions  of  the 
cerebellum,  the  mid-brain  or  Clarke's  column. 

(g)  Polyneuritic  Type. — This  was  recognized  first  by  Medin, 
and  later  by  many  other  observers.  It  is  doubtful,  considering  the 
absence  of  sensory  signs,  whether  the  process  involved  is  a  true 
neuritic  one.  Its  existence  is  not  definitely  proved,  but  the  amount 
of  work  which  has  been  done  in  this  connection  is  not  large.  This 
type  could  be  explained  by  involvement  of  the  central  nervous 
system.  On  clinical  grounds  the  retention  of  this  type  is  justifiable, 
and  later  a  simplification  may  be  possible. 

(Ji)  Meningitic  Type. — The  meningitic  form  is  that  in  which 
the  symptoms  due  to  involvement  of  the  pia  mater  are  the  most 
prominent;  such  are  vomiting,  headache,  pain  in  the  neck,  pain  and 
stiffness  in  the  spine,  and  a  slight  degree  of  opisthotonos.  We  owe 
it  to  Wickman  that  such  cases  were  recognized  as  belonging  to 
Heine-Medin  disease.  Formerly  they  were  classed  as  cerebro- 
spinal meningitis  occurring  with  infantile  paralysis,  and  it  was  even 
suggested  that  cerebrospinal  meningitis  and  infantile  paralysis  wrere 
one  and  the  same  disease.  Later  epidemics  have  led  to  Wickman's 
view  being  upheld.  Xetter  found  that  29  per  cent,  of  his  cases 
belonged  to  the  meningitic  type.  Lhermitte,  as  late  as  1909, 
assumed  a  close  relationship  between  infantile  paralysis  and  cerebro- 
spinal meningitis,  and  he  also  denied  the  connection  between 
epidemic  infantile  paralysis  and  Landry's  disease;  but  he  is  almost 
the  only  observer  who  holds  such  views. 

Prognosis. — For  many  years  Heine's  dictum  held  good,  that 
the  prognosis  quoad  vitam  was  good,  but  the  prognosis  quoad 
sanationem  bad.  At  the  present  time,  owing  to  the  researches  of 
Wickman,  we  would  rather  invert  Heine's  prognosis. 

The    mortality    in    different    epidemics    and    within    the    same 


20 


EPIDEMIC   INFANTILE   PARALYSIS 


epidemic  varies   immensely.        Wickman   found  the   figure   to   vary 
between  10  per  cent,  and  42.3  per  cent. 


Wickman  ... 

Leegaard 
Zappert  ... 
Lindner  and  Mally 
Fiirntratt 
Krause   ... 
Ed.  Muller 
Peiper 
Eichelberg 


Sweden,  1905 
Norway,  1905 
N.  Austria,  1908 
E.  Austria,  1908 
Steiermark,  1908 
Westphalia,  1909 
Hesse-Nassau,  1909 
Pomerania,  1909 
Hanover,  1909 


Total   number 

of  cases  with 

paralysis 


868 

577 
266 

7i 
433 
633 
100 

51 
34 


Mortality 


16.7    per  cent. 

14.56 

10.8 

22.5 

13.6 

12.3 

16 

11. 7 

20.58 


In  this  table  the  mortality  figure  is  in  relation  to  the  cases  with 
paralysis  only;  the  abortive  cases  are  not  included. 

In  general  the  fourth  and  fifth  days  are  the  most  dangerous. 
There  is  further  a  marked  difference  between  the  infantile  and  the 
adult  cases.     Wickman  found:  — 

In  children  up   to    11   years — Mortality   10.5   per  cent. 
In   patients   above    11   years — Mortality  27.6  per  cent. 

The  statistics  of  other  authors  show  a  similar  result. 

In  connection  with  the  prognosis  quoad  sanationcm  the  rela- 
tionship between  the  transitory  abortive  type  and  the  types  with 
paralysis  has  already  been  mentioned. 

Recovery  from  paralysis,  which  was  specially  emphasized  by 
Neurath  in  1901,  occurs  in  at  least  20  per  cent,  of  all  cases 
(Wickman). 

In  this  respect  also  there  is  a  great  difference  between  children 
and  adults. 

Wickman  gives  the  following  :  — 

In  patients  9  to   11   years  old — 48.4  per  cent. 
In  patients  above  11  years  old — 32.2         ,, 

Leegaard  finds  :  — 

In   patients  up    to    14   years — 30.4   per  cent,    recovery 
In   patients   above    14  years — 22.2  ,,  ,, 

The  prognosis  is  from  every  point  of  view  worse  in  adults  than 
in  children. 

Sporadic  Infantile  Paralysis. — Finally,  let  us  consider  the  so- 
called  sporadic  type.  The  more  recent  writers  have  not  only  con- 
sidered the  identification  of  these  cases  with  epidemic  infantile 
paralysis  doubtful,  but  have  denied  this  identity.  They  do  this  on 
the  ground  that  the  clinical  picture  is  quite  different  in  the  two 
cases,  the  paralysis  sets  in  suddenly  without  any  prodromal  sym- 
ptoms,   and   the    cases  occur  in   a   totally   isolated    way.      It   must 


THE    SYMPTOMATOLOGY    OF   THE    DISEASE    IN    MAN  21 

be  remembered,  however,  that  no  case  of  sporadic  poliomyelitis  has 
been  recorded  to  which  a  counterpart  cannot  be  found  among 
epidemic  cases.  Other  undoubtedly  infectious  diseases  occur  in  a 
sporadic  manner,  e.g.,  meningitis  and  scarlet  fever;  further,  it  is 
doubtful  whether  so-called  sporadic  cases  are  ever  really  sporadic, 
owing  to  the  fact  that  the  associated  cases,  being  abortive,  are  over- 
looked. It  has  been  maintained  that  the  prognosis  is  different  in 
the  two  groups,  that  death  and  recovery  from  the  paralysis  never 
occur  in  sporadic  cases.  But  this  means  merely  that  the  fatal  cases 
have  been  called  "  Landry's  paralysis,"  and  those  which  recover 
have  been  called  "  polyneuritis,"  that  the  difference  depends  upon 
an  arbitrary  nomenclature.  However,  at  the  present  time  no  doubt 
can  exist,  as  the  identity  of  the  disease  in  the  sporadic  and  the 
epidemic  forms  is  proved  by  means  of  the  serum  test. 


CHAPTER  III. 

Etiology    of    the    Disease. 


I.— MICROSCOPICAL   AND    CULTURAL 
RESEARCHES    WITH      EXPERIMENTS     ON 

ANIMALS, 

The  older  Views. — The  disease  is  even  now  sometimes  called 
"paralysis  during  dentition"  in  England.  The  views  of  Marshall, 
Kennedy,  and  others  appear  seemingly  still  to  have  some  adherents, 
though  probably  this  is  only  apparent;  they  blamed  difficult  denti- 
tion as  the  cause  of  Heine-Medin  disease.  At  the  present  time  we 
cannot  pass  by  this  theory  without  some  recognition,  particularly  as 
a  larger  clinical  experience  and,  before  all,  experiments  on  animals 
have  taught  us  that  the  mucous  membrane  of  the  mouth,  nose,  and 
throat  is  a  frequent  point  of  entrance  of  the  virus;  and,  moreover, 
as  these  older  physicians  associated  the  beginning  of  the  disease 
with  disturbance  of  the  intestinal  canal.  In  the  oldest  observations 
therefore  we  find  the  same  points  of  entrance  indicated,  which  we 
still  regard  as  the  most  important.  It  was  from  the  English 
writers  that  Heine  took  his  idea  that  difficult  dentition  lay  at  the 
root  of  the  trouble;  or  at  any  rate  he  was  supported  by  them  in  his 
theory.  Such  an  assumption  was  in  accordance  with  the  spirit  of 
the  times ;  men  sought  rather  for  endogenous  than  for  exogenous 
causes  of  disease.  The  disturbances  which  accompany  dentition 
together  with  the  great  developmental  activity  occurring  at  the 
same  time  in  the  central  nervous  system  formed,  according  to 
Heine,  a  sufficient  cause  of  irritation  of  the  delicate  nervous 
system;  an  additional  proof  was  found  in  the  fact  that  inflammation 
of  the  brain  and  spinal  cord  occurred  most  frequently  during  these 
years.  Although  we  cannot  accept  Heine's  theory  in  its  entirety 
to-day,  we  must  admit  that  there  was  some  justification  for  it;  we 
ourselves  know  no  reason  why  Heine-Medin  disease  attacks 
children  specially,  and  occurs  in  certain  years  of  childhood  more 
than  in  others.  In  his  theory  as  to  pathogenesis  Heine  compels 
admiration  for  his  acumen.  He  was  strongly  opposed  to  the  theory 
that  the  disease  was  hereditary  or  due  to  a  defect  in  development; 
this  theory   was  certainly  a  convenient  explanation,   so  convenient 


ETIOLOGY   OF  THE   DISEASE  23 

that  up  to  quite  recent  times  it  has  appeared  in  the  text-books. 
Taking'  into  consideration  the  state  of  medical  knowledge  of  his 
time  we  must  admit  that  his  reasoning  was  not  lacking  in  clarity. 
The  twenty  years  after  Heine's  monographs  produced  nothing  of 
importance.  One  reason  for  this  may  be  found  in  the  rise  of  the 
French  theory  of  an  "essential"  or  "idiopathic"  infantile  para- 
lysis; this  tended  to  make  inquiry  into  the  cause  of  the  disease 
appear  unnecessary,  even  when  pathological  investigation  had 
proved  that  such  a  term  as  "  essential  "  was  quite  unjustifiable. 

Striimpell's  Hypothesis. — We  owe  it  to  the  broad  view  of  the 
subject  taken  by  the  great  clinicians  Strumpell.  Seeligmuller,  and 
Pierre-Marie  that  once  more  attention  was  drawn  to  the  subject  of 
the  etiology  of  the  disease.  The  direction  in  which  they  moved 
proved  to  be  at  once  definite  and  fertile  of  result.  They  started 
from  the  clinical  observation  that  the  whole  clinical  picture  of  the 
disease,  particularly  in  its  early  stages,  showed  great  similarity 
with  other  diseases  which  were  produced  certainly  by  infection 
from  without.  Further,  that  cases  which  appeared  to  be  sporadic 
could  be  arranged  in  groups,  and  consideration  of  the  question 
whether  the  disease  was  not  only  infectious  but  even  contagious 
became  imperative.  I  cannot  do  otherwise  than  quote  some  of 
the  more  pregnant  of  Strumpell's  dicta.  In  1884,  in  his  thesis, 
Strumpell  discusses  the  etiology  of  some  of  the  diseases  of  the 
nervous  system.  He  says:  "Passing  in  review  the  other  nervous 
diseases  from  this  point  of  view,  one  group  stands  out  by  itself, 
the  members  of  which  show  great  similarity  with  one  another  in 
their  course  and  in  their  symptomatology.  This  group  consists  of 
the  acute  multiple  neuritis,  acute  poliomyelitis  and  acute  encephal- 
itis of  children.  All  have  a  sudden  onset  accompanied  by  con- 
siderable fever.  The  patients  show  mental  dulness,  suffer  from 
headache,  gastric  disturbances,  and  occasionally  enlargement  of 
the  spleen,  swelling  of  the  joints,  and  a  slight  albuminuria. 
According"  to  our  present  point  of  view  these  are  all  signs  of 
infection   by  a  pathogenic  organism."* 

In  another  place  Strumpell  says:  "The  peculiar  clinical 
appearances  of  spinal  infantile  paralysis  have  frequently  given  rise 
to  the  opinion  that  in  this  disease  we  have  to  deal  with  an  acute 
infective  process.  As  in  the  case  of  so  many  undoubtedly  infec- 
tious diseases,  we  cannot  prove  this  to  be  so  by  direct  demonstration 
of  the  causative  agent.  At  present  we  can  rely  only  upon  the 
following  facts:  The  peculiarity  of  the  clinical  course:  the  sudden 
onset  for  which  no  obvious  cause  is  present;  the  moderately  high 
temperature;  the  severity  of  the  general  symptoms;  finally,  the 
nature  of  the  changes  found  in  the  spinal  cord,  which  point  unmis- 
takably to  a  truly  inflammatory  process." 

Seeligmiiller  and  Pierre  Marie  bring  forward  similar  arguments 
to  prove  that  the  disease  is  due  to  a  specific  infection.     How  little 

*  In  the  original  not  italicized. 


24  EPIDEMIC   INFANTILE   PARALYSIS 

general  acceptance  was  given  to  these  arguments  is  proved  by  the 
rejection  of  the  theory  of  infection  by  so  important  an  authority  as 
Dejerine  even  as  late  as  the  year  1888;  he  maintained  that  clinically 
and  pathologically  the  disease  belonged  to  the  group  of  system 
diseases. 

Nevertheless,  when  on  the  report  of  an  epidemic  (about  1881) 
there  followed  more  and  more  announcements  of  epidemics  of 
infantile  paralysis,  the  probability  of  an  infective  basis  of  the 
"disease  became  greater,  and  from  that  time  dates  the  era  of  active 
etiological  investigation  along  bacteriological  lines,  particularly 
after  the  publication  of  Medin's  famous  investigations  in  1890. 

Microscopical  and  Cultural  Investigation. — Attention  had 
already  been  directed  to  the  spinal  cord  as  possibly  harbouring 
bacteria.  Goldscheider  in  1893  had  stained  the  cord  of  an  acute 
case  with  methylene  blue  and  by  Gram's  method,  and  failed  to  find 
any  bacteria.  Siemerling  and  Dauber  obtained  similar  negative 
results ;  their  negative  findings  were  confirmed  repeatedly  by  other 
observers.  These  results,  obtained  by  using  well-recognized 
bacterial  stains,  made  observers  chary  of  accepting  later  positive 
findings  obtained  by  means  of  cultural  methods.  By  some  the 
difficulty  was  overcome  by  assuming  that  bacteria  were  destroyed 
very  rapidly  in  the  grey  substance  of  the  cord. 

The  Era  Of  Cocci. — Schultze,  by  describing  a  case  which 
clinically  gave  evidence  of  considerable  involvement  of  the  men- 
inges, began  this  era  which  I  have  called  the  era  of  cocci,  because 
of  the  nature  of  the  organism  which  was  found.  He  found,  on 
examination  of  the  lumbar  puncture  fluid,  "  many  diplococci, 
arranged  in  rows,  similar  to  gonococci  but  having  the  appearances 
of  the  meningococcus  of  Weichselbaum  and  Jager."  It  was 
remarkable  that  all  attempts  to  culture  these  organisms  failed, 
although  they  were  numerous,  and  although  cultures  were  made 
from  other  samples  of  the  lumbar  puncture  fluid.  Upon  these 
facts  Schultze  constructed  a  theory  of  the  identity  of  meningitis 
and  poliomyelitis;  he  regarded  the  two  diseases  as  due  to  different 
localization  of  the  same  morbid  agent. 

Following  on  this,  many  positive  results  were  obtained  by 
bacteriological  examination,  and  it  appears  as  though  the  discovery 
of  Schultze  had  exercised  a  certain  influence  upon  later  observers. 
Bulow-Hansen  and  Harbitz  (in  1898)  also  found  a  Gram-positive 
diplococcus  in  the  cerebrospinal  fluid,  but  do  not  lay  much  stress 
upon  their  discovery  on  account  of  the  very  numerous  negative 
results  which  they  obtained.  Courmont  and  Bonne  (1899),  Concetti 
(1900),  Dercum  (1900),  Looft  and  Dethloff  (1901),  Gossage  (1902), 
Engel  (1900),  Spiller  (1903),  Batten  (1904),  Barnes  and  Miller  (1907) 
all  found  micro-organisms  which  were  considered  to  be  meningo- 
cocci in  some  cases,  pneumococci  or  staphylococci  in  others.  These 
results  served  to  strengthen  the  theory  of  the  microbial  origin  of 
the  disease.  Giersvold's  observations  during  the  first  great  Nor- 
wegian epidemic  in  1905  and  1906  caused  a  considerable  sensation; 


ETIOLOGY   OF  THE   DISEASE  25 

he  found  Gram-positive  cocci  shaped  like  beans  and  forming  short 
chains,  which  he  believed  to  be  identical  with  the  Jager  meningo- 
coccus. These  organisms  grew  on  the  ordinary  culture  media. 
Harbitz  and  Scheel  were  obviously  influenced  by  these  results;  they 
also  found  cocci  in  the  cerebrospinal  fluid,  but  reserved  judgment 
as  to  their  exact  etiological  significance. 

A  study  of  the  literature  shows  that  in  no  case  has  any  clear 
proof  of  the  causal  significance  of  the  cocci  observed  been  brought 
forward;  further,  the  bacteria  seen  have  been  of  the  most  various 
kinds,  they  have  been  observed  only  in  isolated  cases,  and  no  inocu- 
lation experiments  have  been  made  with  any  of  them. 

The  Accumulation  of  Negative  Results. — Doubts  as  to  the 
importance  of  the  few  positive  results  become  much  greater  when 
we  compare  them  with  the  vast  number  of  negative  results  obtained. 
Guinon  and  Rist  in  1903  found  the  cerebrospinal  fluid  of  an  epidemic 
case  to  be  sterile,  and  with  the  advent  of  the  larger  epidemics  in 
Scandinavia  (1905-1907),  North  America  (1907-1908),  Austria  (1908- 
1909),  Germany  (1909J,  and  France  (1909)  the  negative  evidence  has 
become  overwhelming.  In  Sweden  Wickman  and  Jundell  not  only 
found  eight  perfectly  fresh  specimens  of  lumbar  puncture  from 
different  cases  sterile,  but  also  all  material  obtained  from  autopsies 
on  cases  of  epidemic  Heine-Medin  disease.  Ellermann  also 
obtained  only  negative  results,  but  fell  into  the  error  of  proclaiming 
certain  rhizopods  to  be  the  cause  of  poliomyelitis;  his  statements 
did  not  hold  good  in  the  face  of  criticism.  In  America  the  results 
obtained  by  many  experimenters  were  all  negative — Purkins  and 
Dudgeon,  Sherman  and  Spiller,  Greene,  Wilson  and  Rothrock, 
Thomas,  Taylor,  Hoch,  Wollstein,  Starr,  and  Stephens.  For 
example,  out  of  226  cases  Stephens  obtained  a  culture  in  only  seven 
cases,  and  these  he  recognized  definitely  as  contaminations.  There 
were  no  positive  results  in  France.  The  first  observers  had  found 
cocci  which  were  in  no  way  difficult  of  demonstration  or  of  culture, 
and  this  gave  further  importance  to  the  consistently  negative  results 
obtained  from  a  far  greater  material,  and  led  to  the  opinion  that 
the  original  discoveries  were  due  to  errors  in  technique.  One  such 
error  was  explained  by  Leiner  and  v.  Wiesner,  who  found  that  if 
only  the  first  portion  of  the  lumbar  puncture  fluid  was  used  a 
growth  of  cocci  could  be  obtained  fairly  frequently,  but  never  from 
the  rest  of  the  fluid;  they  carried  out  the  same  experiment  in  the 
case  of  diseases  other  than  infantile  paralysis,  and  obtained  the 
same  result,  thus  proving  that  the  positive  results  were  due  to  mere 
contamination,  probably  from  the  skin  of  the  patient.  They  also 
pointed  out  the  danger  of  using  broth  cultures  in  this  connection, 
because  bacteria  will  flourish  in  the  broth  without  giving  any  indi- 
cation of  the  number  originally  present.  Koch's  axiom  is  still 
more  or  less  justified,  namely,  that  for  proof  of  the  etiological 
significance  of  any  organism  it  must  be  shown  to  be  present  in  a 
quantity  proportionate  to  the  severity  of  the  clinical  signs. 

So   far,   therefore,   the   history  of  the  search  for  the   cause   of 


26  EPIDEMIC   INFANTILE  PARALYSIS 

Heine-Medin  disease  is  a  succession  of  mistakes.  A  short  historical 
retrospect  is  not  without  its  advantages  if  we  learn  from  it  the 
great  danger  of  accepting  any  results  in  a  scientific  inquiry  with 
undue  haste.  I  have  alluded  above  to  my  own  impression,  that  it 
was  the  expressed  or  unexpressed  underlying  conviction  that  epi- 
demic infantile  paralysis  was  only  a  form,  differently  localized,  of 
epidemic  cerebrospinal  meningitis  which  led  observers  to  consider 
bacteria  as  the  cause  of  a  disease  which  we  know  now  has  nothing 
to  do  with  them.  The  experiments  carried  out  under  these  con- 
ditions only  confirmed  them  in  their  view.  At  this  point  I  would 
draw  attention  particularly  to  Wickman's  conclusions;  at  a  time 
when  nothing  was  known  for  certain  of  a  non-bacterial  cause  of 
the  disease,  and  when  there  were  many  adherents  of  the  theory  of 
the  identity  of  meningitis  and  poliomyelitis,  he  stated  definitely,  on 
the  basis  of  thorough  pathological,  clinical,  and  epidemiological 
investigation,  that  if  cocci  were  really  the  cause  of  both  diseases 
they  must  be  fundamentally  biologically  different  in  the  two  cases. 

Personal  Bacteriological  Research, — I  cannot  deny  that  when 
I  began  to  study  this  disease  at  a  time  when  my  clinical,  patho- 
logical and  epidemiological  experience  was  limited,  I  was  under  the 
influence  of  the  hypothesis  that  meningitis  and  infantile  paralysis 
might  be  identical,  or,  at  any  rate,  related  diseases;  as  a  result,  in 
my  first  bacteriological  experiments  I  devoted  my  energies  to  the 
finding  of  cocci.  Owing  to  the  fact  that  in  our  Hessian  epidemic 
the  respiratory  tract  was  the  site  of  the  prodromal  symptoms, 
whereas  in  the  Westphalian  epidemic  studied  by  Krause  it  was  the 
alimentary  tract  which  suffered  first,  I  was  led  to  make  cultures 
from  the  pharynx  and  tonsils.  The  results  disclosed  the  ordinary 
organisms;  in  the  first  experiments  I  found  pneumococci  to  be 
somewhat  in  excess  of  normal,  and  in  the  later  cases  the  staphylo- 
coccus albus;  under  the  influence  of  the  above-mentioned  hypo- 
thesis I  spent  considerable  time  in  investigating  the  latter  organ- 
isms. On  turning  my  attention  to  the  cerebrospinal  fluid  the 
problem  became  clearer;  specimens  were  obtained  from  chronic, 
very  acute,  severe,  and  slight  cases,  and  always  the  result  was 
negative.  The  specimens  were  quite  clear;  vigorous  centrifugali- 
zation  gave  not  a  trace  of  deposit;  with  the  microscope  a  few 
lymphocytes  were  seen;  an  organic  virus  was  not  seen  either  in 
stained  or  in  unstained  specimens.  The  stains  used  were  of  the 
most  various  kinds,  the  usual  aniline  dyes.  Gram's  stain,  Ziehl's 
stain  for  Bacillus  tuberculosis,  Giemsa's  stain.  Many  culture  media 
were  used :  Bouillon,  gelatine,  agar,  glycerine-agar,  g"rape-sugar- 
agar,  ascites-agar,  agar  with  the  addition  of  the  sera  of  different 
animals,  coagulated  serum,  &c.  Equal  parts  of  lumbar  puncture 
fluid  and  bouillon  were  mixed  and  incubated  at  a  temperature  of 
37°  C.  The  result  of  the  tests  was  that  the  tubes  remained  sterile 
except  in  a  few  instances.  The  growth  in  these  cases  could  be 
identified  always  as  a  common  contamination.  Examination  of  the 
blood  in  a  severe  case  led  to  the  same  result. 


ETIOLOGY   OF  THE  DISEASE  27 

It  must  be  admitted  that  these  experiments,  together  with  the 
results  obtained  by  others,  did  net  furnish  proof  that  the  disease 
was  not  caused  by  a  micro-organism;  it  was  not  known  for  certain 
whether  the  virus  existed  in  the  blood  or  in  the  cerebrospinal  fluid; 
indeed,  later  experiments  on  animals  have  shown  that  the  virus 
exists  at  most  in  extremely  small  quantities  in  either  of  these  fluids. 
Certainty  could  be  attained  only  after  examination  of  the  central 
nervous  system,  in  which  a  living  virus,  if  present  at  all,  would  be 
found. 

The  material  I  used  for  this  investigation  was  obtained  from 
children  who  had  died  from  the  effects  of  a  typical  attack  of  Heine- 
Medin  disease.  The  details  of  the  cases  I  will  give  later  when 
describing  the  experiments  on  animals.  Cultures  were  made  from 
the  brain,  the  pons,  and  the  spinal  cord,  which  were  placed  at  my 
disposal  by  Professor  Beneke.  The  tubes  remained  sterile  except 
in  a  few  instances  of  contamination.  Careful  search  in  stained 
sections  revealed  no  bacteria  although  the  pathological  appearances 
were  typical  of  poliomyelitis.  Inasmuch  as  the  later  experiments 
on  animals  proved  that  the  virus  was  present  in  large  amount  in 
the  affected  portions  of  the  nervous  system  I  was  able  to  state  with 
confidence  that  it  was  impossible  that  a  microbe  which  could  be 
stained  and  cultivated  easily  could  be  tlic  active  agent  in  the  causa- 
tion of  epidemic  infantile  paralysis. 

I  have  mentioned  already  the  researches  of  Wickman  which 
had  led  to  the  same  result;  there  followed  the  work  of  Landsteiner, 
and  particularly  the  wide  researches  of  Krause  and  Meinicke,  who 
throughout  the  whole  Westphalian  epidemic  never  found  any 
bacteria  which  could  be  regarded  as  playing  a  part  in  the  etiology 
of  the  disease. 

All  these  researches,  of  great  importance  but  all  negative, 
brought  about  unanimity  of  opinion  in  1909  that  a  bacterial  cause 
of  Heine-Medin  disease  does  not  exist;  it  was  like  a  voice  from 
the  past  when  Pottpeschnigg  in  October,  1909,  announced  the  dis- 
covery of  a  coccus  with  some  claims  to  be  considered  pathogenic, 
but  he  very  soon  acknowledged  that  the  coccus  was  merely  a  con- 
tamination. 

Important  Microscopical  Findings. — Although  ordinary  bac 
teriological  methods  were  thus  proved  unavailing  it  was  not  thereby 
made  certain  that  the  microscope  and  culture  tubes  would  not  ulti- 
mately yield  results.  As  will  be  demonstrated  later,  the  virus 
belongs  to  the  variety  which  is  capable  of  passing  through  the 
filters  of  Berkefeld,  Chamberland,  and  Pukall,  which  keep  back 
ordinary  bacteria.  Starting"  from  this  fact  it  was  necessary  to  seek 
the  virus  in  filtrates  which  were  free  from  the  normal  cellular 
constituents  of  brain  and  spinal  cord.  With  Joseph  and  Siebert  I 
examined  such  filtrates  by  means  of  the  ultramicroscope.  We 
found  very  small,  oval,  slightly  illuminated  bodies  which  were 
motionless  or  showed  only  Brownian  movements;  they  attracted  our 
attention  because  we  did  not  find  them  in  filtrates  of  normal  brain. 


28  EPIDEMIC   INFANTILE  PARALYSIS 

From  experience  gained  in  previous  ultramicr.oscopic  investigations 
of  proteins  we  were  able  to  exclude  the  theory  that  these  bodies 
were  due  to  coagulation  of  albumin.  On  the  other  hand,  the 
appearance  of  these  bodies  was  not  constant  enough  to  enable  us 
to  state  that  they  were  connected  with  the  disease,  or  that  they  were 
the  actual  causative  agent.  The  observation  is,  however,  of 
importance,  because  Flexner  observed  similar  bodies  at  a  later  date, 
and  his  description  corresponds  very  closely  with  our  own  observa- 
tions. Flexner  says  also  that  he  was  able  to  render  these  bodies 
visible  by  means  of  LdfHer's  stain.  Levaditi  had  previously 
obtained  the  same  result;  by  means  of  a  "  culture  "  which  we  shall 
describe  later,  he  had  obtained  small  rounded  bodies  which  he 
succeeded  in  staining  by  Loffler's  method,  and  also  with  weak  solu- 
tions of  fuchsin;  he  expressed  himself  with  regard  to  the  interpre- 
tation of  his  results  in  the  same  guarded  way  as  we  had  done  with 
ours.  Leiner  and  v.  Wiesner  assert  that  they  have  seen  "  very 
small  oscillating  bodies  "  in  a  hanging-drop  preparation  made  from 
virus-containing  filtrate.  They  also  state  that  they  are  not  con- 
vinced that  the  bodies  represent  the  virus  itself. 

Specific  Intracellular  Bodies. — In  yet  another  direction  the  use 
of  microscopic  methods  seems  to  give  some  promise  of  success. 
Wickman  has  drawn  the  analogy  between  poliomyelitis  and  rabies 
as  a  result  of  his  excellent  pathological  investigations.  This 
analogy  becomes  only  more  striking  the  more  the  nature  of  the 
active  agent  is  considered.  Negri  has  called  attention  to  certain 
intracellular  bodies,  which  are  found  only  in  the  ganglion  cells  in 
hydrophobia,  and  are  characteristic  of  this  disease.  There  is  still 
much  discussion  as  to  whether  these  bodies  are  to  be  considered 
the  cause  of  the  disease,  cellular  degeneration  products,  or  merely 
the  capsules  of  the  pathogenic  agent  which  is  as  yet  unknown. 
Wickman  looked  for  similar  intracellular  appearances  in  cases  of 
epidemic  infantile  paralysis,  but  failed  to  find  them.  However,  a 
recent  discovery  makes  it  probable  that  renewed  search  is  justifiable. 
Joest  has  shown  that  Borna's  disease  in  horses,  which  occurs  in 
epidemics,  is  a  disseminated,  infiltrative  myelo-encephalitis;  this 
disease  is  so  similar  to  Heine-Medin  disease  in  its  histological 
appearances — due  allowance  being  made  for  difference  in  localiza- 
tion, Borna's  disease  attacking  the  olfactory  lobe,  and  Heine- 
Medin  disease  the  grey  matter  of  the  anterior  horns — that  one 
might  almost  regard  the  two  diseases  as  being  identical.  Joest 
with  Degen,  using  Mann's  method  of  staining,  demonstrated  the 
presence  of  intranuclear  bodies  in  the  ganglion  cells  in  cases  of 
Borna's  disease;  the  nature  of  these  bodies  is  not  understood  as 
yet,  but  they  appear  to  be  specific  to  the  disease.  At  a  meeting  of 
the  Medical  Society  of  Marburg  (November  3,  1909)  I  stated  my 
belief  that,  in  view  of  Joest's  and  Degen's  results,  it  would  be  of 
value  to  investigate  cases  of  poliomyelitis  using  the  same  methods. 
In  spite  of  most  energetic  search,  however,  Joseph  and  myself  have 
been    unable    to    find    any    constant    intracellular    bodies    either    in 


ETIOLOGY   OF  THE   DISEASE  29 

sections  or  in  smear  preparations  made  from  human  material,  or 
from  the  brain  and  cord  of  infected  apes.  Leiner  and  v.  Wiesner, 
Landsteiner  and  Levaditi  have  carried  out  similar  researches,  and 
have  arrived  at  the  same  negative  result. 

On  the  other  hand,  Bonhoff  found  bodies  included  in  the  nuclei 
of  the  glia  cells,  particularly  of  the  lumbar  enlargement,  of  a  case 
of  undoubted  poliomyelitis,  which  bodies  he  considers  specific;  they 
were  demonstrated  only  by  using  Lentz's  modification  of  Mann's 
stain  applied  to  sections.  The  size  varied  from  a  very  small,  red 
dot  to  an  oval  with  a  diameter  of  3  to  4  ^  ;  the  average  size  had  a 
diameter  of  2  fi.  Occasionally  as  many  as  five  bodies  were  found 
in  one  nucleus;  they  were  surrounded  by  a  clear  zone,  and  the  largest 
of  them  showed  one  or  two  minute  granules  which  stained  clearly 
with  the  Mann-Lentz  method.  Similar  bodies  were  found  in  the 
nuclei  of  cells  forming  the  adventitia  of  the  blood-vessels,  of  the 
ependymal  cells,  and  in  some  nuclei  of  the  round-celled  infiltration. 
In  specimens  made  from  the  spinal  cord  in  normal  cases  and  in 
other  diseases  these  bodies  were  not  found.  Without  going  into 
the  question  whether  these  bodies  represent  one  form  of  the  cause 
of  the  disease,  Bonhoff  claims  that  they  are  abnormal  and  charac- 
teristic of  Heine-Medin  disease. 

"  Cultures  "  Of  the  Vims. — I  said  above  that  attempts  to  culti- 
vate the  virus  of  Heine-Medin  disease  might  not  be  without  value, 
even  though  one  might  be  of  the  opinion  that  the  cause  of  the 
disease  was  not  a  bacterium.  It  is  well  known  that  certain  trypano- 
somes,  which  are  classed  usually  among  the  animal  organisms,  can 
be  grown  on  specially  prepared  media.  I  will  at  once  confess  that 
none  of  my  own  attempts  have  yielded  the  smallest  result,  even 
with  the  media  which  Flexner  and  Lewis  described  later.  These 
authors  at  first  stated  that  they  had  obtained  no  cultures  of  what 
could  be  considered  to  be  a  virus  of  poliomyelitis ;  later  they 
reported  certain  "  cultures  "  which  they  claimed  to  have  obtained. 
They  made  an  emulsion  of  an  infected  spinal  cord,  filtered  this 
through  a  Berkefeld  filter,  and  added  the  filtrate  to  equal  parts  of 
ordinary  bouillon  and  of  human  serum  (in  some  cases  the  serum  of 
rabbits  was  used).  After  a  few  days  they  found  some  opacity  in 
the  tubes;  when  injected  into  apes  these  "cultures"  produced  the 
typical  picture  of  experimental  poliomyelitis.  Levaditi  confirmed 
this  experiment,'  but  it  proves  only  that  after  being  kept  for  a  certain 
time  (for  fifteen  days  in  Levaditi's  case)  at  a  temperature  of  370  C. 
the  fluid  still  contained  the  active  virus  of  poliomyelitis.  The  mere 
fact  of  virulence  does  not  prove  growth  of  the  virus;  it  may  be  that 
the  degree  of  dilution  with  serum-bouillon  was  not  enough  to 
prevent  the  activity  of  the  virus,  and  Flexner  and  Lewis  themselves 
have  proved  that  it  is  possible  to  cause  disease  and  death  in  apes 
with  much  more  dilute  virus.  Flexner  and  Levaditi  state  that  they 
obtained  a  cloudiness  in  a  second  series  of  tubes  inoculated  from 
the  first,  but  that  from  these  secondary  tubes  they  were  unable  to 
produce    the    disease    in    monkeys,    so    that    they    themselves    are 


30  EPIDEMIC   INFANTILE   PARALYSIS 

cautious  in  their  interpretation  of  the  remarkable  appearances 
observed  by  them.  As  we  ourselves  have  never  been  able  to  see 
any  clear  evidences  of  growth  of  the  virus  in  any  media,  and  as 
Leiner  and  v.  Weisner  have  had  the  same  experience,  it  may  well 
be  wise  to  doubt  whether  the  cloudiness  observed  by  Flexner  and 
Lewis  can  be  considered  as  a  culture  at  all,  specially  as  these 
authors  themselves  are  exceedingly  cautious  in  so  describing  it. 
It  may  be  mentioned  that  the  attempts  to  intensify  the  virus  in 
collodion  capsules  in  vivo  by  Leiner  and  v.  Wiesner  have  failed 
also. 

All  investigation  into  the  etiology  of  the  disease  has  shown 
that  the  active  agent  cannot  be  a  bacterium,  nor  can  it  be  any 
micro-organism  capable  of  being  cultivated  easily.  We  have  no 
evidence  which  will  bear  the  test  of  criticism  as  to  the  morpho- 
logical characteristics  of  the  virus. 

Experiments  on  Animals* — The  earlier  experiments  on  animals 
were  few,  but  caused  less  confusion  than  the  supposedly  positive 
bacteriological  results.  At  a  time  when  it  was  still  doubtful 
whether  the  disease  was  infectious  the  aim  of  all  experiments  on 
animals  was  to  find  out  if  any  materials  would  produce  myelitic 
lesions  in  animals  comparable  to  those  of  Heine-Medin  disease  in 
man.  The  first  experiments  were  carried  out  on  rabbits,  a  point 
on  which  I  would  lay  particular  stress.  Roger  infected  fourteen 
rabbits  intravenously  with  streptococci,  and  found  that  in  two  to 
three  weeks  the  animals  wasted,  and  showed  marked  atrophy  in  the 
muscles  of  the  hind  limbs  almost  exclusively,  but  without  any 
definite  paralysis.  Histologically  changes  were  found  in  the 
anterior  horn  cells;  the  number  of  cells  was  diminished,  they  were 
irregular  in  shape,  and  showed  vacuolation  with  degeneration  of 
the  nuclei  in  some  cases.  The  vessels  were  full  and  enlarged,  and 
in  places  there  were  small  haemorrhages.  Roger  concluded  that  a 
more  or  less  systematized  myelitis  could  be  caused  by  an  infective 
agent.  In  the  same  year  Gilbert  and  Lion  made  similar  experi- 
ments on  rabbits,  using  B.  coli.  In  those  animals  which  did  not 
die  very  shortly  paralysis  occurred  on  about  the  twelfth  day  and 
at  the  same  time  diarrhoea.  In  these  cases  also  degeneration  of 
the  anterior  horn  cells  and  hypersemia  were  found.  Vincent 
obtained  similar  results  in  a  rabbit  infected  with  a  mixture  of 
bacteria.  Thoinot  and  Masselin  in  1894  carried  out  the  most  com- 
plete experiments  (Hoche  gives  a  complete  bibliography).  Out  of 
forty-three  rabbits  infected  with  B.  coli  four  died  rapidly.  The 
thirty-nine  survivors  all  suffered  from  paralysis,  generally  of  the 
hind  limbs,  with  muscular  atrophy  and  general  wasting.  Rabbits 
infected  with  staphylococci  were  affected  in  the  same  way.  Vacuo- 
lation of  the  anterior  horn  cells  was  found  but  no  interstitial  change, 
while  the  vessels  zvere  normal. 

Hoche  succeeded  in  producing  changes  in  the  spinal  cord  by 
direct  arterial  infection  with  pneumococci,  staphylococci,  and 
B.  coli  only  when  at  the  same  time  he  injected  starch  or  lycopodium 


ETIOLOGY   OF  THE   DISEASE  3 1 

granules  or  some  other  powdery  material  which  would  produce 
embolic  lesions  in  the  cord.  In  his  case  the  changes  were  all  of  a 
parenchymatous  type  affecting  only  the  cells  and  nerve  fibres,  the 
blood  vessels  being  affected  only  very  slightly  and  the  interstitial 
tissues  not  at  all.  Homen  also  failed  to  obtain  any  results;  he  made 
very  numerous  experiments  with  streptococci,  injecting  them 
specially  into  the  lymph  spaces  and  intraneurally.  Wickman  used 
strains  of  bacteria  which  had  been  passed  repeatedly  through 
animals,  but  he  was  forced  to  admit  that  no  definite  palsy  occurred 
in  any  of  his  animals,  although  they  wasted  considerably;  his  cases 
on  section  also  did  not  show  the  appearances  of  true  poliomyelitis. 
We  must  confess  that  all  these  experiments  produced  very  little 
of  value  in  giving  an  answer  to  the  question  whether  the  changes 
of  poliomyelitis  were  due  to  an  infective  agent.  Judging  from  the 
descriptions  and  illustrations  given  by  the  various  authors,  the 
microscopical  changes  observed  had  very  little  similarity  with  those 
presented  by  the  lesions  of  true  poliomyelitis,  in  spite  of  the 
occasional  changes  seen  in  the  ganglion  cells.  The  characteristic 
adventitious  and  perivascular  cell  infiltration  is  absent,  as  also  the 
increase  in  the  number  of  nuclei,  which  is  so  typical  in  the  sections 
in  cases  of  Heine-Medin  disease.  If  any  comparison  with  a 
spontaneous  disease  is  permissible  it  is  with  progressive  muscular 
atrophy;  this  disease,  however,  is  certainly  totally  different  in  its 
etiology  to  Heine-Medin  disease. 

Although  we  cannot  lay  so  much  stress  on  the  results  of  these 
earlier  experiments  on  animals  as  was  claimed  for  them  at  the  time, 
yet  they  prove  one  fact  very  clearly :  Bacteria  of  very  different 
kinds,  by  whatever  route  they  enter  the  body,  do  not  tend  to 
produce  lesions  typical  of  poliomyelitis.  If  further  proof  that 
bacteria  do  not  cause  the  disease  were  needed,  the  numerous 
negative  results  recorded  above  might  be  interpreted  in  that  sense. 

A  further  point  is  that  rabbits  are  peculiarly  liable  to  suffer 
from  paralyses  when  any  molecular  substance  is  injected  into  the 
blood-stream.  As  we  shall  see  later,  this  observation  is  of  import- 
ance when  considering  the  rabbit  as  an  animal  for  experimental 
research  in  poliomyelitis. 

The  attempts  to  produce  poliomyelitis  in  animals  by  injecting 
material  from  the  organs  of  cases  of  Heine-Medin  disease  will  be 
further  considered  below. 

II.— EXPERIMENTAL  RESEARCH  ON  POLIO- 
MYELITIS IN  MONKEYS— CLINICAL  HISTORY 
OF  EXPERIMENTAL  POLIOMYELITIS. 

Landsteiner's  Original  Experiment. — In  the  case  of  successful 
research  with  animals  there  is  a  definite  point  where  this  branch 
of  the  subject  begins.  Landsteiner,  with  the  aid  of  Popper,  has 
the   credit   of  having   for  the   first   time   succeeded   in   transmitting 


32  EPIDEMIC   INFANTILE  PARALYSIS 

the  disease  to  monkeys.     Landsteiner  published  his  results  in  full 
in  the  Zeitschrift  fur  Immunitatsforschung  on  April  5,   1909. 

I  give  a  full  abstract  of  his  results  owing  to  their  great 
importance  :  — 

The  material  used  was  the  spinal  cord  of  a  child  of  9  years,  who  died 
on  the  fifth  day  of  an  attack  of  typical  Heine-Medin  disease.  An  emulsion 
was  made  and  this  was  injected  into  the  peritoneum  of  two  monkeys.  The 
first,  a  young  Cynoce-plialus  hamadryas,  became  seriously  ill  on  the  sixth 
day  and  died  on  the  eighth.  At  the  autopsy  the  internal  organs  were  found 
to  be  normal  with  the  exception  of  the  spinal  cord  which  was  seriously 
affected.  The  conditions  found  were  :  Infiltration  of  the  pia  mater  of  the 
cord  with  cells,  perivascular  infiltration  in  the  grey  matter,  diffuse  infiltra- 
tion in  the  grey  matter  which  was  disorganized  by  oedema;  the  anterior 
horns  were  much  more  affected  than  the  posterior  ones.  Similar  inflam- 
matory infiltrations  were  found  in  the  medulla,  pons,  mid-brain  and  cortex. 
The  cells  of  the  infiltration  were  mostly  lymphocytes.  Where  inflammation 
was  present  the  ganglion  cells  were  much  altered,  and  chiefly  in  the 
anterior  horns  (outline  blurred,  granular  disintegration,  vacuolization,  nuclei 
staining  poorly,  invasion  by  round  cells). 

In  the  second  monkey,  a  young  Macacus  rhesus,  between  the  twelfth 
and  seventeenth  day  paralysis  appeared,  which  became  complete  in  both 
lower  limbs.  The  changes  found  were  similar  but  less  marked  to  those 
obtaining  in  the  first  monkey.  The '  animal  was  killed  on  the  nineteenth 
day.  Two  more  monkeys  were  injected  with  emulsion  of  the  spinal  cord 
of  this  monkey,  but  the  experiment  was  without  result. 

The  description  given  of  the  illness  of  the  second  monkey 
and  of  the  histological  appearances  in  both  cases,  also  the  illus- 
trations of  the  histological  changes,  leave  no  doubt  that  Landsteiner 
and  Popper  succeeded  in  producing  poliomyelitis  in  monkeys,  which 
ran  a  course  similar  to  the  disease  in  man  and  caused  lesions 
identical  from  the  histological  point  of  view. 

The  probability  that  the  disease  was  caused  by  a  living  virus 
was  increased  by  these  experiments  and  would  have  become  a 
certainty  if  the  attempt  to  transmit  the  disease  to  a  further  series 
of  monkeys  had  been  successful.  As  this  failed  entirely  the 
possibility  was  not  excluded,  that  the  disease  might  be  transmitted 
by  a  non-living  agent  {e.g.,  a  toxin).  Landsteiner  and  Popper 
reject  this  theory  on  the  ground  that  the  histological  changes  had 
all  the  characters  of  an  inflammatory  process.  They  explain  the 
failure  of  the  attempt  to  transmit  the  disease  further  by  suggesting 
that  the  potency  of  the  virus  was  diminished  by  its  passage  through 
one  animal.  We  may  say  at  once  that  another  and  better  explana- 
tion may  be  brought  forward,  namely,  that  the  intraperitoneal 
route  of  infection  is  unsatisfactory  and  cannot  be  depended  upon 
to  give  results.  Experiments  made  by  Knopf elmacher  and  by 
Strauss  and  Huntoon  can  be  explained  in  the  same  way;  in  these 
instances  also  monkeys  were  infected  with  human  virus,  but  the 
attempt  to  inoculate  further  monkeys  failed. 

Personal  Experiments  with  Monkeys. — The  repeated  failures 


ETIOLOGY   OF  THE   DISEASE  33 

to  transmit  the  disease  from  ape  to  ape  indicated  that  there  was 
some   factor  in  the  question   which   was   as  yet  unknown. 

When  I  began  to  perforin  experiments  myself,  I  had,  of 
course,  Landsteiners  experience  before  me;  but  I  took  advantage 
also  of  Pasteur's  work  on  "  Hydrophobia."  I  have  already  drawn 
attention  to  the  analogy  which  exists  between  poliomyelitis  and 
rabies.  Wickman  had  shown  the  close  similarity  of  the  histological 
changes  in  the  two  diseases.  My  own  researches  had  convinced 
me  that  poliomyelitis  was  not  caused  by  bacteria  and  that  the 
virus,  like  that  of  rabies,  showed  a  selective  preference  for  the 
central  nervous  system.  One  of  the  first  points  in  Pasteur's  work 
was  the  discovery  of  a  practically  certain  method  of  transmitting 
the  disease  from  animal  to  animal.  Anyone  who  knows  the 
history  of  his  work  knows  what  a  definite  advance  was  made 
by  the  discovery  of  a  new  and  certain  technique  for  infecting  the 
animals.  Pasteur  used  subdural  or  intracerebral  injection  of  the 
virus.     I  chose  intracerebral  injection  into  monkeys. 

The  technique  is  extremely  simple.  The  monkey  is  enveloped  in  a 
towel;  an  assistant  holds  the  head;  the  head  is  shaved  over  an  area  the 
size  of  a  crown ;  the  operation  is  performed  over  the  central  gyri  on  one 
side  or  the  other,  and  in  skilled  hands  does  not  require  an  anaesthetic.  An 
incision  not  more  than  3  mm.  long  is  made  through  the  scalp  down  to  the 
bone ;  the  skull  is  perforated  with  a  small  bore  in  a  few  seconds  ;  a  little 
practice  enables  one  to  go  through  the  skull  without  piercing  the  dura. 
The  needle  of  a  small  syringe  filled  with  the  virus  is  then  passed  into  the 
hole  made  by  the  bore,  through  the  dura  and  into  the  brain  to  a  depth  of 
about  ii  cm.  ;  not  more  than  .5  to  .6  c.cm.  of  the  emulsion  is  injected  slowly. 
The  needle  is  rapidly  withdrawn,  a  small  plug  of  gauze  is  pressed  firmly 
on  the  wound  for  a  short  time  and  the  wound  then  closed  with  collodion. 
The  whole  operation  must  be  carried  out  with  carefully  sterilized  instru- 
ments. 

By  means  of  this  intracerebral  method  I  was  able  at  once  to 
produce  a  disease  in  monkeys  which  was  clinically  and  pathologically 
identical  with  poliomyelitis  in  man;  I  was  able  also  to  transmit 
the  disease  from  one  monkey  to  another.  This  proved  t licit  the 
virus  which  caused  the  changes  in  the  brain  and  spinal  cord  ZL'as 
living  and  not  merely  a  toxin.  Considering  that  we  and  others 
had  proved  that  it  was  impossible  to  cultivate  the  virus  on  artificial 
media,  it  was  of  the  greatest  importance  that  a  means  of  cultivating 
it  in  vivo  had  been  discovered.  In  order  that  virus  and  disease 
could  be  investigated  experimentally,  it  was  essential  that  some 
method  of  cultivating  the  virus  by  means  of  transmission  from 
one  animal  to  another  should  be  available. 

I  reported  my  experiments  in  November,  1909,  to  the  Medical 
Society  of  Marburg  and  published  them  shortly  afterwards  in  the 
Munchcncr  mcd.  Wochenschrift.  I  believed  at  the  time  that  I 
was  the  first  to  succeed  in  transmitting  the  disease  from  one 
animal  to  another.  However,  at  the  same  time,  and  partly  before 
me,    but   all   during   the   month   of   November,    1909,    other   results 


34  EPIDEMIC   INFANTILE  PARALYSIS 

proving'  the  same  point  were  published — Flexner  and  Lewis,  on 
November  13;  Leiner  and  v.  Wiesner,  on  November  18;  and  finally 
Landsteiner  and  Levaditi,    on  November  27,    1909. 

(a)  SOURCE  OF  THE  VIRUS  USED  IN   MY  EXPERIMENTS. 

The  original  material  was  obtained  from  the  brains  and  spinal 
cords  of  patients  who  died  from  poliomyelitis  during  the  epidemic 
of  the  autumn  of  1909  in  Hesse-Nassau.  To  remove  all  doubt  as 
to  the  fact  that  the  cause  of  death  was  poliomyelitis  I  append  the 
full  clinical  and  post-mortem  records  of  the  cases.  The  clinical 
notes  were  written  by  Professor  Dr.  Muller,  the  pathological 
reports  by  Professor  Dr.  Beneke,  who  have  kindly  allowed  me  to 
make  use  of  them  here.  They  have  already  appeared  in  a  mono- 
graph by  Professor  Muller. 

I. — Julie  M.,  aged  6  years,  from  Frankfort.  History  given  by  Dr. 
Veupel  in  Frankfort. 

The  patient  attended  school  up  to  the  date  of  her  illness.  No  other 
source  of  infection  known.  On  November  3  she  became  suddenly  ill  with 
a  high  temperature  (30/60  C),  listlessness,  anorexia,  furred  tongue,  vomiting, 
and  constipation.  She  had  pain  in  the  neck,  was  restless  at  first,  later 
drowsy ;  marked  sweats,  but  no  particular  tenderness.  She  complained  only 
of  pain  in  the  neck  and  throat,  and  when  she  sat  up  she  asked  that  her 
head  might  be  supported.     No  sphincter  trouble. 

When  examined  on  the  third  day  the  child  could  not  cry  (there  is  no 
record  of  other  bulbar  symptoms),  arms  normal,  marked  meteorism,  flaccid 
paralysis  of  both  legs,  deep  reflexes  absent.  A  short  time  before  death  she 
rolled  her  eyes  and  was  unable  to  cry  or  speak.  Death  occurred  during  the 
evening. 

Autopsy  on  November  6,  1909  :  — 

Development  normal ;  rigor  mortis  present ;  moderate  cyanosis ;  marked 
-post-mortem  staining ;  fat  well  developed ;  muscles  dry ;  muscles  of  the 
thigh  soft  and  of  a  light  grey-red  colour;  calf-muscles  dry,  dark  red-grey 
colour,  firm. 

Thorax. — A  few  drops  of  fluid  in  pericardium.  Heart-muscle  firm, 
light  grey-red  colour,  no  marked  degeneration.  Lungs  engorged ;  no 
pleurisy,  no  local  lesions. 

Trachea. — Markedly  red  along  whole  length;  no  exudate;  marked 
bronchitis,  with  much  mucus  in  the  larger  branches. 

Larynx. — Normal. 

Tonsils. — On  both  sides  double  the  normal  size,  not  projecting,  light- 
grey  in  colour,  covered  with  slight  grey  inflammatory  exudate. 

CEsophagus. — Nil.     Thyroid. — Nil. 

Abdomen. — Spleen  slightly  enlarged,  soft,  friable,  dark  red-grey> 
follicles  numerous. 

Kidneys  and  suprarenals. — Nil,  the  former  are  slightly  more  red  than 
normal. 

Genital  organs. — Nil. 

Liver. — Large,  soft,  dull,  red-grey  in  colour,  with  many  ischaemic 
subcapsular  areas. 

Stomach. — Contains  partially  digested  food  and  some  mucus.  Mucous 
membrane  rather  dull,  soft  and  red. 


ETIOLOGY   OF  THE   DISEASE  35 

Intestine. — Normal  colour  and  contents ;  the  follicles  in  both  small  and 
large  intestine  are  increased  in  size;  Peyer's  patches  are  prominent  and 
certainly  enlarged. 

Cerebrospinal  fluid  obtained  by  lumbar  puncture  was  copious,  slightly 
cloudy  and  colourless.     A  few  drops  of  fluid  in  the  ventricles  of  the  brain. 

Brain  and  spinal  cord. — Moist,  soft;  the  grey  matter  looks  somewhat 
red.  No  oedema  of  the  pia ;  no  haemorrhages;  no  extradural  oedema;  no 
gross  local  lesion  in  the  anterior  horns  of  the  spinal  cord  grey  matter. 

Microscopical  examination:  — 

(i)  Dorsal  spinal  cord. — Moderate  infiltration  of  the  pia;  vessels  much 
engorged.  Marked  infiltration  of  the  ventral  median  fissure.  Considerable 
infiltration  of  anterior  horns;  posterior  horns  affected  to  a  less  degree. 
Ganglion  cells  seen  only  in  Clarke's  column.  In  all  sections  the  white 
matter  shows  perivascular  infiltration ;  a  similar  condition  found  in  the 
cervical  cord.  In  many  places  the  limits  of  the  infiltration  mark  off  the 
grey  from  the  white  matter  in  a  very  striking  way. 

(2)  Medulla  oblongata. — Slight  infiltration  of  the  pia ;  marked  peri- 
vascular infiltration  around  the  larger  vessels;  much  scattered  infiltration, 
here  and  there  clearly  affecting  the  region  of  ganglion  cells.  Olives 
practically   unaffected.     Marked  enlargement   of  perivascular  lymphatics. 

(3)  (a)  Brain. — In  the  neighbourhood  of  the  great  ganglia  some  peri- 
vascular infiltration ;  here  and  there  some  subependymal  infiltration,  in 
places  almost  forming  abscesses,  which  is  not  connected  with  ganglion  cells. 

(b)  Cortex. — Pia  not  affected;  slight  oedema  of  the  vessel  sheaths;  no 
infiltration. 

Pathological  diagnosis. — Poliomyelitis  spin.  cerebral;  tonsillitis; 
rhinitis  post.  ;  tumour  lien.  ;  hypertroph.  follicul.   intest. 

From  Professor  Beneke  I  received  portions  of  the  pons  and 
of  the  lumbar  cord;  of  each  of  these  a  piece  the  size  of  a  pea 
was  emulsified  in  8  c.cm.  of  the  cerebrospinal  fluid  of  the  case.  A 
monkey  weighing"  1,970  gm.  (mangabey  monkey,  No.  1)  was  given 
an  intracerebral  injection  of  this  emulsion.  The  monkey  died  on  the 
eighth  day  after  showing  signs  of  paralysis  (for  details  vide  infra). 
An  emulsion  of  the  spinal  cord  was  injected  into  a  second  monkey 
intracerebrally  (mangabey,  No.  2).  This  animal  became  ill  on  the 
tenth  day,  and  died  on  the  eleventh. 

The  virus  thus  obtained  will  be  called  p.m.   virus   No.  6. 

II. — Karl  Schn.,  aged  2!  years,  from  Marburg.  No  family  history  of 
nervous  disease.  Parents  and  brothers  and  sisters  remained  well  during 
the  patient's  illness.  The  child  had  suffered  from  a  club-foot,  which  had 
been  operated  upon  previously,  and  from  furunculosis  following  vaccination 
otherwise  well.  He  attended  an  infant  school  where  he  came  in  contact 
with  children  from  the  suburb  Weidenhausen.,  which  was  an  affected  area. 
A.  few  weeks  ago  the  mother  met  a  woman  with  her  child  who  had  suffered 
from  an  attack  of  poliomyelitis  some  months  previously.  The  father  is  a 
shoemaker  with  an  open  shop,  says  that  recently  he  has  not  worked  for 
families  in  which  there  was  any  poliomyelitis,  that  he  has  not  had  any 
visits  from  or  paid  visits  in  any  infected  area. 

The  child  became  ill  on  November  22  with  a  high  temperature  and 
rigor;  much  wandering  and  restlessness;  sleepless,  occasional  jerking  of 
the  limbs  and  starting  up  in  bed. 


36  EPIDEMIC   INFANTILE  PARALYSIS 

The  mother  reports  that  sweating  was  profuse.  The  child  complained 
that  he  "  could  not  move  "  when  he  was  lifted  up,  cried  a  great  deal  when 
put  on  the  chamber.  On  November  23  very  little  urine  was  passed,  and  the 
child  was  unable  to  stand  or  walk  alone,  fell  when  he  was  put  on  his  feet, 
and  "  was  quite  slack  like  an  idiot." 

Examination  on  November  24. — Very  pale,  apathetic.  Cranial  nerves 
not  affected.  Slight  bronchitis,  pulse-rate  increased.  The  body  is  remark- 
ably flaccid;  the  child  cannot  sit  up;  epigastric  reflexes  only  just  obtained. 
Movements  of  the  upper  limbs  are  good;  marked  fine  tremor  of  the  hands 
even  when  at  rest.  Child  cannot  stand  or  walk;  falls  down  when  put 
on  his  feet.  On  the  right  side  club-foot  which  has  been  operated  upon. 
Deep  reflexes  are  still  present  on  both  sides;  plantar  reflex  present.  All 
movement  or  touching  of  the  legs  causes  pain.      Leucopenia  is  present. 

November  25. — High  temperature  (39' 5°  C.).  Great  restlessness  and 
general  collapse.  Very  pale;  apathetic;  alas  nasi  move  with  respiration;  no 
herpes;  no  membrane  on  the  throat;  no  marked  swelling  of  the  glands  of 
the  neck.  Resonance  diminished  at  the  left  base  with  bronchial  breathing, 
vocal  resonance  present;  marked  general  bronchitis  with  dyspnoea, 
although  intercostals  do  not  act  and  respiration  seems  to  be  entirely 
diaphragmatic.  Abdomen  soft;  some  tympanites;  abdominal  reflexes 
absent.  The  muscles  of  the  limbs  are  generally  hypotonic ;  there  is  no 
definite  localized  paralysis;  the  deep  reflexes  are  present  but  diminished. 
Lumbar  puncture  :  copious  clear  sterile  fluid,  showing  a  few  lymphocytes 
on  centrifugalization.  Death  occurred  in  the  evening;  the  child  was  con- 
scious, but  unable  to  cry  up  to  the  last. 

Autopsy  on  November  2g  :  — 

Well-built  child,  aged  2I  years ;  pale ;  moderate  degree  of  club-foot ; 
slight  rickets;  muscles  soft. 

Thorax  (opened  from  behind). — Heart  strong  and  not  obviously  degen- 
erate. Upper  lobe  of  left  lung  slight  emphysema ;  lower  lobe  grey-red  in 
colour,  pneumonic ;  bronchi  contain  some  pus  and  mucus ;  right  lung  normal. 

Spleen  normal  in  size,  moist.  Kidneys  normal  in  size  and  shape, 
microscopic  examination  normal.  Blood  taken  from  the  left  pulmonary 
vein  contains  Diplococcus  lanceolatus,  but  in  addition  a  considerable  number 
of  organisms  of  the  nature  of  spirochsetes,  staining  feebly  with  Loffler  and 
showing  feeble  movements;  some  have  granules  like  streptococci;  also  a  few 
grey  oval  bodies  showing  extremely  active  karyokinesis.  The  leucocytes 
do  not  show  karyokinesis  ;  it  is  confined  to  these  large  cells  which,  on  the 
other  hand,  contain  no  fat  globules.  Red  blood-cells  normal.  In  the 
bronchial  secretion  exclusively  Frankel's  diplococcus  was  found.  Blood 
from  spleen,  heart  and  spinal  cord  contained  no  bodies  like  spirochaetes  or 
like  the  oval  bodies  described  above. 

The  capillaries  of  the  lung  where  it  is  not  inflamed  contain  many 
polymorphonuclear  leucocytes.  In  the  inflamed  parts  there  is  rather  an 
absence  of  leucocytes.  In  the  larger  arteries  and  veins  of  the  lungs  the 
blood  contains  mainly  lymphocytes,  leucocytes  being  rare.  The  pneumonic 
infiltration  contains  many  leucocytes,  the  exudate  being  serous  rather  than 
suppurative. 

Heart. — The  musculature  shows  no  abnormality ;  there  is  no  infiltration. 

Spleen. — Follicles  markedly  enlarged;  the  central  portion  is  large  with 
many  degenerate  nuclei ;  the  periphery  is  comparatively  free  from  degenera- 
tion. Many  follicles  are  composed  almost  completely  of  germinal  areas 
with  practically  no  peripheral  portion.  Spleen  pulp  hyperaemic,  generallv 
disintegrated  and  poor  in  cells. 


ETIOLOGY   OF  THE   DISEASE  37 

Kidneys. — Slight  signs  of  irritation  in  the  convoluted  tubules ;  no  other 
pathological  appearances. 

The  dura  contains  a  small  amount  of  fluid.  Spinal  cord  firm,  white 
matter  normal,  grey  matter  everywhere  red. 

Dorsal  region  of  the  cord. — Slight  infiltration  of  the  pia ;  infiltration 
more  marked  around  the  vessels  in  the  anterior  longitudinal  bundle,  most 
marked  in  the  vessels  of  the  anterior  horns  and  in  the  anterior  portion 
of  the  lateral  tracts.  Central  canal  normal.  Diffuse  infiltration  of  both 
anterior  horns,  they  are  small  and  show  only  traces  of  the  ganglion  cells. 
Definite  oedema.  Clarke's  column  quite  unaffected,  ganglion  cells  normal. 
In  the  white  matter  some  local  lesions.  Ganglion  cells  are  found  practically 
not  at  all  throughout  the  anterior  horns.  Occasionally  a  normal  ganglion 
cell  is  seen. 

Pathological  diagnosis. — Poliomyelitis  acuta;  pneum.  lob.  inf.  pulm. 
sin.  ;  bronchitis  purulenta. 

From  the  lumbar  cord  a  5  per  cent,  emulsion  was  made  in 
normal  saline  and  injected  on  the  same  day  into  the  brain  of  a 
Macacus  rhesus  (No.  4).  The  amount  used  was  '3  c.cm.  The 
monkey  remained  well ;  on  December  2  and  3  it  seemed  to  us  that  he 
did  not  care  about  using"  his  right  fore  limb,  but  this  weakness 
gradually  disappeared.  It  is  possible  that  this  was  one  of  the 
abortive  cases  which  are  seen  in  man  frequently. 

Thus  it  was  not  possible  to  transmit  the  disease  from  this  case 
of  undoubted  poliomyelitis  to  a  monkey  in  a  manner  which  was 
devoid  of  doubt.  The  question  whether  we  should  have  succeeded 
if  we  had  used  more  monkeys  cannot  be  discussed.  The  fault  did 
not  lie  with  the  animal  (No.  4),  because  at  a  later  date,  and  with  a 
different  virus,  it  died  rapidly  with  paralysis.  One  point  may  be 
mentioned  :  that  the  lumbar  cord  was  not  examined  microscopically 
as  the  dorsal  cord  had  been. 

III. — Karl  D.,  aged  2!  years,  from  Arfurt.  Report  from  Dr.  Hartmann, 
of  Villmar  a.  d.  Lahn.  Nothing  known  of  method  of  infection.  No  illness 
in  the  family  or  neighbourhood  ;  no  mortality  among  animals.  The  family 
had  not  left  their  premises  during  the  last  few  weeks,  nor  had  they  had 
visitors.  The  nearest  place  where  cases  of  poliomyelitis  have  occurred 
recently  is  two  kilometres  distant. 

The  child  became  ill  on  November  29.  Fever,  lassitude,  one  attack 
of  vomiting.  Cough  and  restlessness ;  no  sweats  or  hyperesthesia.  On  the 
fourth  day  palsy  of  the  neck  and  left  arm;  no  affection  of  the  bulb  or 
cranial  nerves.  On  the  next  day  the  right  arm  and  leg  were  attacked.  The 
muscles  of  both  legs  were  flaccid  and  the  deep  reflexes  absent.  Death  on 
the  sixth  day  (December  2). 

Autopsy  on  December  4,   1909  : — ■ 

Well-developed  child;  cyanosis  slight;  fat  well  developed;  muscles  soft, 
rather  pale. 

Heart  and  lungs. — Normal. 

Spleen  very  large,  tense,   dark  black  red  in  colour,  firm  and   dry. 

Kidneys  and  liver  dull,  engorged,  otherwise  normal. 

Intestines. — Marked  hypertrophy  of  the  follicles. 

Mucous  membrane  of  the  stomach  smooth,  fairly  thick,  very  red, 
covered  with  thick  layer  of  pus  and  mucus. 


38  EPIDEMIC   INFANTILE   PARALYSIS 

Organs  of  the  throat  normal. 

Tonsils  and  glands  in  the  neck  small,  pale. 

Pancreas. — Normal. 

Peridural  fat  normal.  Spinal  cord  soft.  Sections  show  definite  red  dis- 
coloration of  the  grey  matter,  which  is  shrunk  and  softened.  White  matter 
is  bulky  and  moist. 

Dura  is  tense.  Pia  not  cedematous,  markedly  red,  the  whole  brain  is 
of  a  diffuse  red  colour. 

Microscopical  examination  :  — 

(1)  Dorsal  region. — No  infiltration  of  the  pia.  Little  infiltration  in  the 
anterior  longitudinal  fissure;  rather  more  in  the  anterior  horns  and  adjacent 
white  matter.  Central  canal  in  places  infiltrated  with  small  round  cells; 
anterior  horns  small,  cells  almost  absent;  a  diffuse  patchy  infiltration  with 
mononuclear  and  polymorphonuclear  cells.  Clarke's  column  unaffected; 
no  other  infiltration. 

(2)  Cervical  region. — Widespread,  well-marked  infiltration  of  the 
anterior  horns;  in  places  a  few  ganglion  cells  remain.  Moderate  hyperaemia, 
slight  oedema,  marked  infiltration  of  the  vessel  sheaths.  In  the  rest  of  the 
cord  only  a  slight  diffuse  cell  infiltration. 

(3)  Medulla  oblongata. — Ependyma  raised  slightly  by  oedema;  marked 
perivascular  infiltration  in  the  subependymal  region  and  round  the  larger 
vessels.  A  diffuse  fairly  well-marked  cell  infiltration  not  directly  related 
to  any  particular  cell  group.      Olives  and  ventral  part  of  sections  unaffected. 

(4)  Pons. — Slight  infiltration  round  larger  vessels;  a  few  local  lesions 
found  in  pons  and  in  cerebellar  peduncles.  Cerebellar  convolutions  normal. 
The  large  cell  nuclei  of  the  pons  are  remarkably  free  from  disease,  which 
is  most  marked  around  the  aqueduct  and  the  larger  vessels  in  this  region. 
Ventral  portion  unaffected. 

(5)  Thalamic  region. — Marked  linear  infiltration  round  the  vessels. 
Ganglion  cells  in  the  neighbourhood  of  the  infiltration  are  destroyed;  other 
areas  of  ganglion  cells  unaffected. 

(6)  Cerebral  cortex. — Only  a  few  scattered  cells  in  the  pia;  perivascular 
lymph  spaces  much  enlarged  ;  no  definite  infiltration. 

(7)  Hippocampus. — Relatively  large,  in  places  marked,  vascular  in- 
filtration, also  general  diffuse  infiltration. 

Pathological  diagnosis. — Poliomyelitis  acuta;  enlargement  of  the 
spleen  ;   acute  gastritis ;  renal  and  hepatic  degeneration. 

A  5  per  cent,  emulsion  was  made  from  the  lumbar  cord  and 
injected  as  follows:  — 

The  monkey  No.  8  (Cercopithecus  ruber)  received  an  intra- 
cerebral injection  of  '4  c.cm. ;  it  remained  well  until  December  15, 
1909;  on  the  16th  it  became  weak  in  the  hind-limbs,  there  was 
tremor  of  the  head,  and  the  monkey  was  depressed.  On  the  17th 
general  condition  improved,  but  the  paresis  of  the  hind-limbs  was 
more  marked.  The  paresis  began  to  improve  on  the  18th  and 
disappeared  by  the  21st  (?  abortive  poliomyehtis). 

Monkey  No.  9  (Cercopithecus  fuliginosus)  was  given  1  c.cm. 
subcutaneously,  and  remained  healthy.  It  was  observed  until 
February  15,   1910. 

Monkey  No.  10  (Cercopithecus  fuliginosus)  had  '2  c.cm.  injected 
direct  into  the  left  sciatic  nerve,  and  remained  entirely  healthy  up 
to  January  15,   1910. 


ETIOLOGY  OF  THE  DISEASE  39 

Monkey  No.  6  (Macacus  rhesus)  received  -8  c.c.  of  a  2-5  per 
cent.  solution  which  had  passed  through  a  Berkefeld  filter,  injected 
into  the  brain.  It  remained  quite  well  (observed  until  January  5, 
1910). 

No  success  therefore  attended  the  attempts  to  transfer  the 
disease  to  monkeys  by  means  of  the  virus  of  Case  III. 

IV. — Wilhelm  P.,  of  Weifenbach,  near  Biedenkopf,  aged  q  months. 
Admitted  to  hospital  on  December  6,  1909.  The  first  case  of  the  disease 
in  that  village.  Parents  and  three  brothers  and  sisters  quite  well  both 
before  and  during  patient's  illness.  On  November  27  the  child  had  a  boil 
on  the  neck,  which  disappeared  without  medical  treatment.  The  child  is 
still  being  suckled  and  has  had  no  illness.  The  father  is  a  telegraph 
official,  and  has  to  go  about  all  over  the  district.  No  other  possible  source 
of  infection  is  known. 

Onset  of  the  disease  occurred  on  December  2 ;  high  fever,  vomiting, 
anorexia,  somnolent  during  the  day  and  wakeful  at  night.  Diarrhoea.  On 
the  following  night  convulsions,  the  eyes  being  rolled  and  the  face  drawn 
to  the  right  side.  No  stiffness  of  the  neck.  General  tenderness  :  the  child 
objects  when  it  is  touched,  though  it  is  unable  to  cry.  Marked  sweating, 
particularly  of  the  head.     Incontinence  of  urine. 

Examination  on  December  5. — Eyes  normal;  mouth  drawn  over  to  the 
right ;  swallowing  difficult ;  bronchitis ;  other  organs  normal ;  abdomen  soft ; 
abdominal  reflexes  absent ;  cremasteric  reflexes  absent. 

Hypotonia  of  all  extremities;  both  arms  and  legs  paralysed.  Deep 
reflexes  all  absent. 

Lumbar  puncture. — 12  c.c.  of  clear,  sterile  fluid  under  considerable 
pressure.     Centrifugalized  showed  a  few  lymphocytes. 

December  6. — No  improvement ;  passing  much  mucus ;  much  dyspnoea  ; 
during  the  night  suffocative  attacks  requiring  artificial  respiration. 

December  7. — Pulse  fair ;  respiration  diaphragmatic.  Heart  improved 
after  a  second  lumbar  puncture.  During  the  evening  collapse  aiid  death 
from  respiratory  failure. 

Autopsy  on  December  7. 

Well-developed  child ;  marked  -post-mortem  staining.  Rigor  mortis 
fairly  well  marked;  scars  of  punctures  in  the  back.  Muscles  of  the  bad: 
dry  and  soft. 

Extradural  connective  tissue  oedematous. 

Abdominal  organs  normal. 

Spleen  small,  rather  shrivelled,  but  full  of  blood.  Thymus  large ;  clear 
fluid  in  pericardium;  heart  full  of  clots,  firm  and  dark-red  musculature. 
No  demonstrable  degeneration.  Left  lung  very  hyperaemic,  more  so  in 
lower  lobe,  soft,  contains  air.  Some  mucus  in  bronchi ;  mucous  membrane 
pale.  Right  lung  almost  entirely  collapsed ;  bronchi  do  not  contain  much 
mucus ;  the  mucous  membrane  is  pale. 

Parotid  gland  normal.  Glands  in  neck  normal.  Tonsils  small ;  no 
sign  of  inflammation ;  base  of  tongue  and  mouth  the  same. 

Larynx  and  trachea  normal.  Thyroid  normal.  Upper  portion  of 
pharynx  somewhat  swollen;  nasal  mucous  membrane  slightly  red  and 
covered  with  pus.  Inferior  turbinate  much  swollen  with  mucopurulent 
catarrh  above.  The  upper  portion  of  the  nasal  cavity,  together  with  the 
septum,  show  only  slight  redness  of  the  mucous  membrane. 

Intestines    are    distended    with    gas;    in    the   lower    part    a    ■post-mortem 


40  EPIDEMIC   INFANTILE   PARALYSIS 

invagination.  Lymph  nodules  remarkably  enlarged,  containing  many 
malformed  nuclei.  The  larger  lymphatics  in  many  places  distended  with 
lymphocytes. 

Appendix. — Shows  condition  similar  to  that  of  ileum;  much  lymphoid 
tissue;  lymphatics  distended  with  lymphocytes;  many  wander  cells  in  the 
lymph  nodules. 

Adrenals  are  small  and  pale;  kidneys  deep  red-grey  in  colour,  full  of 
blood,  no  obvious  degeneration. 

Liver  small;  on  section  rather  dull  and  dry;  microscopical  interstitial 
infiltration  ;  some  apparent  increase  in  wander  cells,  which  here  also  tend 
to  form  rows  of  cells ;  no  abscess  formation. 

Microscopical  examination  : — ■ 

Lymphatic  glands. — Germ  centres  much  developed,  with  extraordinary 
number  of  malformed  and  degenerate  nuclei  of  wander  cells.  Lymph 
channels  packed  with  lymphocytes. 

Thymus. — Hypersemic,  but  not  otherwise  abnormal. 

Spleen. — The  germ  centres  of  the  follicles  are  large,  and  contain  many 
malformed  nuclei.  Many  follicles  contain  only  germ  centres.  Pulp 
relatively  poor  in  cells. 

Testis. — Normal;  no  infiltration.  Epididymis  the  same.  Blood-vessels 
normal. 

Bone-marrow  (from  vertebras). — Structure  very  dense,  full  of  cells; 
hypertrophied.      Fairly  numerous  leucocytes;  a  few  giant  cells. 

The  middle  part  of  the  spinal  cord  removed  for  bacteriological  pur- 
poses. The  rest  shows  marked  redness  and  softness  of  the  grey  matter,  the 
white  matter  being  of  a  relatively  firm  consistency.  Considerable  subdural 
haemorrhages  in  the  form  of  flat,  soft  coagula.  Pia  very  hypersemic  in  the 
region  of  the  right  anterior  vein.  The  ventricles  appear  empty.  (Edema 
of  the  extradural  connective  tissue.  The  brain  firm  and  moist.  Cerebral 
cortex  rose-coloured ;  marked  venous  hyperasmia  in  cortex,  white  matter 
and  large  ganglia ;  no  oedema  of  the  pia.  The  base  of  the  brain,  particu- 
larly the  medulla,  is  very  red.  Sections  through  the  pons  and  cerebellar 
peduncles  show  moderate  hyperaemia.  Consistency  of  the  medulla  prac- 
tically normal ;  the  colour  of  the  grey  matter  is  normal. 

Cerebrum. — In  the  region  of  the  uncinate  gyrus,  both  in  the  cortex  and 
the  white  matter,  many  separate  wander  cells  of  various  shapes.  The  pial 
vessels  are  filled  in  places  with  leucocytes,  which  almost  constitute  a 
thrombus.     Xo  abscess. 

Convexity. — Moderate  infiltration  of  the  pia ;  slight  oedema  of  the 
perivascular  lymph  spaces;  everywhere  degenerate  wander  cell  nuclei;  no 
well-defined  lesion  or  marked  infiltration. 

Pes  hippocampi. — Everywhere  wander  cells  and  small  infiltrations, 
chiefly  subependymal;  vessels  hypersemic;  many  leucocytes  sometimes 
causing  a  thrombus;  a  similar  condition  in  a  few  instances  in  the  veins  of 
the  choroid  plexus. 

Microscopical   examination   of  the   cord   and   brain   stem  :  — 

Lumbar  region. — Marked  infiltration  of  the  vessel  sheaths.  Consider- 
able cell  infiltration  in  the  anterior  longitudinal 'fissure.  Anterior  horns 
on  both  sides  show  great  infiltration  and  oedema  of  the  vessel  sheaths,  with 
wander  cells  of  various  shapes.  A  few  ganglion  cells  are  present;  these  do 
not  appear  changed.  In  the  rest  of  the  section  only  a  slight  perivascular 
infiltration.      Nerve  roots  normal. 

Dorsal  region. — Infiltration  is  less  in  degree,  but  similar  in  dis- 
tribution. Anterior  horn  cells  are  in  many  cases  atrophic,  but  are  not 
invaded  by  leucocytes. 


ETIOLOGY   OF   THE   DISEASE  41 

Cervical  region. — Similar  to  lumbar  region.  Hypersemia  well  marked; 
much  oedema  and  infiltration  of  the  anterior  horns.  The  wander  cells  have 
nuclei  of  a  remarkably  long,  thread-like  shape. 

Medulla  oblongata. — Much  perivascular  infiltration  in  the  region  of 
the  ependyma ;  also  some  diffuse  infiltration  in  that  region.  A  few  wander 
cells  present  all  over  the  section,  also  in  the  olives,  of  an  elongated  shape 
and  fairly  numerous. 

Pons. — Considerable  pial  infiltration  at  the  base  where  the  vessels  con- 
tain a  large  number  of  leucocytes.  A  fair  number  of  long-shaped  wander 
cells.  Xear  the  aqueduct  both  infiltrations  and  wander  cells  are  more 
numerous;  the  infiltration  is  in  the  form  of  local  collections  of  cells,  the 
ganglion  cells  in  the  neighbourhood  being  quite  well  preserved. 

Pathological  diagnosis. — Acute  poliomyelitis;  collapse  of  the  lung; 
follicular  catarrh  of  the  intestines. 

Five  per  cent,  emulsions  were  made  from  the  lumbar  cord,  the 
dorsal  cord  and  the  brain  in  the  region  of  the  basal  ganglia.  They 
were  used  for  inoculation  in  the  following  manner:  — 

Monkeys  (tf)  and  (b)  (both  Ccrcopithccus  fuliginosus)  received 
an  intracerebral  injection  of  '5  c.c.  on  December  7,  1909.  Monkey 
(a)  became  ill  on  the  14th  and  died  on  the  15th.  Monkey  (b) 
sickened  on  the   15th  and  died,  typically  paralysed,   on  the   16th. 

'5  c.c.  of  a  1  in  10  dilution  of  the  original  emulsion  was  injected 
intracerebrally  into  monkey  Xo.  11  (Macacus  rhesus).  Paralysis 
set  in  on  December  20,  1909,  and  death  occurred  on  January  11, 
1910. 

The  virus  obtained  from  Case  IV  is  referred  to  as  virus  Xo.  11, 
and  was  made  the  basis  of  many  further  injections  into  monkeys. 

V. — Heinrich  R.,  aged  3,  from  Schweinsberg.  Parents  and  other 
children  well  both  before  and  during  illness  of  patient.  Child  at  school 
up  to  date  of  illness.      Xo  other  possible  source  of  infection  known. 

December  11. — Fever,  headache,  anorexia,  vomiting.  Sleep  restless, 
much  crying  out  and  tossing  in  bed.  Head  retracted;  spine  held  stiff. 
When  taken  hold  of  child  complained  much  of  pain.  Xo  respiratory  or 
intestinal  trouble ;  no  sweats. 

December  12. — Examination  at  the  medical  clinic.  Remarkable  dermo- 
graphia  over  the  whole  body.  Eyes  and  cranial  nerves  normal.  Difficulty 
in  swallowing ;  mouth  clear.  Head  and  spine  held  rigid ;  abdomen  soft. 
Possibly  some  paresis  of  the  right  shoulder  muscles;  left  upper  and  both 
lower  limbs  normal.  Deep  reflexes  and  plantar  reflexes  present.  Kernig's 
sign  positive. 

December  13. — Much  headache;  rigidity  of  head  and  spine  more 
marked.  At  noon,  sudden  attack  of  dyspnoea,  with  failure  of  pulse  and 
cyanosis.  The  head  fell  limply  to  the  right  side.  Towards  evening  tracheal 
rales.  Paralysis  of  muscles  of  respiration.  X-ray  examination  showed  that 
only  the  left  half  of  the  diaphragm  was  still  acting.  Oxygen  improved 
the  pulse.  Later  respiration  became  more  embarrassed.  Deep  reflexes 
abolished  in  all  limbs.  Epigastric  reflexes  present.  Death  from  respiratory 
paralysis.     Lumbar  puncture  and  brain  puncture  had  proved  useless. 

December  14. — Autopsy. 

"Well-developed  child;  fat  abundant;  muscles  well-developed;  skin  pale. 

Xo  degeneration  in  the  muscles. 


42  EPIDEMIC   INFANTILE   PARALYSIS 

Lungs.— Pleura  clear.  Many  large  areas  of  collapse  in  both  lungs. 
Much  frothy,  yellow-brown  mucus  in  the  bronchi.  Very  slight  redness  of 
mucous  membrane.  Pharynx,  larynx,  and  trachea  normal.  Spleen 
moderate  in  size,  tense,  firm,  dark  red.  Liver  small,  soft,  contains  fair 
amount  of  blood,  rather  dull.  Adrenals  small,  elongated,  and  soft.  Kidneys 
engorged,  otherwise  normal.  Stomach  contains  much  thick  yellow-brown 
mucus,  with  many  black  thread-like  clots.  Many  small  haemorrhages  in 
the  mucosa,  which  is  red.  All  lymphatic  tissue  in  the  intestinal  tract  is 
swollen;  mucous  membrane  red  in  places.  Pancreas  and  urogenital  tract 
normal.     The  spinal  cord  was  removed  whole. 

On  section  the  grey  matter  was  distinctly  more  red  than  normal.  The 
white  matter  moist  and  swollen.  Over  the  brain  the  dura  was  tense.  Over 
the  right  parietal  region  a  superficial  haemorrhage  about  the  size  of  a  five- 
shilling  piece.  The  whole  brain  engorged;  the  white  matter  universally 
rose-coloured.  Ventricles  empty;  not  enlarged.  The  pons  definitely 
hyperaemic. 

Microscopical  examination  :  — 

Medulla. — Slight,  definite  perivascular  infiltration  of  the  subependymal 
vessels.  In  the  substance  of  the  medulla  many  disseminated  infiltrations 
with  elongated  and  degenerate  cell  nuclei.  Some  of  these  infiltrations  are 
of  considerable  size. 

Ganglion  cells  which  are  implicated  in  these  infiltrations  show 
degeneration,  and  are  attacked  by  leucocytes.  In  the  region  of  the  olives, 
and  generally  in  the  deepest  parts  of  the  sections,  no  infiltration. 

Pons. — The  basal  pia  shows  cell  proliferation ;  no  perivascular  infil- 
tration in  the  pia,  but  much  in  the  region  of  the  iter  and  fourth  ventricle, 
both  perivascular  and  diffuse.  Wander  cells  are  few  except  in  the  infiltrated 
parts. 

Cerebellum. — Pia  almost  unaffected ;  here  and  there  small  infiltrations ; 
cortex  and  medulla  free  of  inflammation. 

Ganglia  of  mid-brain. — Some  slight  subependymal  cedema ;  some 
indications  of  perivascular  infiltration ;  in  places  a  suggestion  of  local 
infiltration. 

Spleen. — Well-developed  follicles  with  large  germ  centres.  In  these 
markedly  malformed,  elongated,  and  degenerate  nuclei,  but  no  definite 
necrosis.      Here  and  there  slight  hyaline  degeneration. 

Pathological  diagnosis. — Acute  poliomyelitis ;  collapsed  lung ;  acute 
gastritis;  follicular  catarrh  of  the  intestines. 

A  20  per  cent,  emulsion  was  made  from  about  equal  portions 
of  the  brain  stem,  the  medulla  oblongata,  and  the  dorsal  region  of 
the  cord.  Monkeys  Nos.  13  and  14  received  '5  c.c.  intracerebrally, 
and  at  the  same  time  3  c.c.  into  the  peritoneum.  Xo.  13  became 
paralysed  on  December  26,  and  died  on  January  5;  Xo.  4  was  para- 
lysed by  December  23,  and  died  on  December  24.  On  histological 
examination  typical  poliomyelitis  was  found  in  both  cases.  The 
virus  obtained  from  Case  V  will  be  called  .Virus  Xo.  12;  it  was 
passed  through  many  animals. 

The  Susceptibility  of  Monkeys  to  the  Virus  of  Poliomyelitis..— 
We  succeeded  in  transmitting  the  disease  to  monkeys  in  three  out  of 
five  human  cases ;  we  were  able  to  transmit  the  disease  to  other  mon- 
keys in  these  cases.  In  two  cases  the  disease  could  not  be  transmitted. 
I  can  give  no  satisfactory  reason  why  this  was  the  case.     I  consider 


ETIOLOGY   OF  THE   DISEASE  43 

that  the  possibility  has  not  been  excluded,  that  the  parts  of  the  cord 
selected  were  affected  but  slightly  by  the  disease,  and  consequently 
contained  only  a  small  amount  of  virus.  One  result  of  the  experi- 
ments is  that  in  any  single  case  of  poliomyelitis  it  is  advisable  to 
inoculate  several  monkeys  either  intracerebrally  only  or  together 
with  an  intraperitoneal  injection.  It  is  not  justifiable  to  draw  the 
conclusion  that  it  is  possible  to  infect  only  three-fifths  of  all 
monkeys.  For  such  a  purpose  a  much  larger  number  of  animals 
would  have  to  be  used.  In  that  case  I  believe  that  a  much  larger 
percentage  of  animals  would  be  found  to  be  susceptible  to  the 
disease,  considering  that  at  the  time  we  made  our  experiments  our 
knowledge  of  the  technique  of  inoculation  was  in  its  infancy.  At 
the  same  time  Leiner  and  v.  Wiesner  have  reported  lately  that  out 
of  six  cases  they  were  able  to  infect  monkeys  in  only  three. 

The  figures  of  re-inoculation  from  monkey  to  monkey  are  quite 
different.  Taking  all  the  experiments  together,  in  which  sufficient 
doses  of  virus  were  given  to  unaffected  monkeys  by  cerebral  injec- 
tion, the  results  are  as  follows  :  Out  of  forty-two  monkeys  thirty- 
eight  became  paralysed,  of  which  the  greater  number  died:  in  two 
animals  the  symptoms  were  doubtful,  and  two  remained  quite  well. 
If  the  doubtful  cases  are  added  to  those  which  remained  well  the 
resulting  figure  is  9.8  per  cent,  of  failures;  in  90.2  per  cent,  there- 
fore, infection  followed  at  once.  I  may  mention  that  in  the  cases 
in  which  the  virus  was  injected  into  both  brain  and  peritoneum, 
the  number  of  successes  was  100  per  cent.  My  figures  correspond 
very  closely  with  those  obtained  by  Flexner  and  Lewis  :  Eighty- 
three  monkeys  received  an  intracerebral  inoculation;  of  these 
seventy-seven  became  markedly  paralysed,  two  slightly  paralysed, 
while  four  remained  well,  i.e.,  95  per  cent,  of  successes.  Landsteiner 
and  Levaditi  had  95  per  cent.,  Leiner  and  v.  Wiesner  85  per  cent, 
of  positive  results.  The  latter  authors  found  intraneural  injection 
to  be  as  successful  as  intracerebral. 

I  used  Cercopithecus  fuliginosus,  C.  ruber.  Macacus  rhesus, 
M.  cynomolgus.  and  in  one  instance  a  Tota  monkey.  Flexner 
and  Lewis  found  that  M.  nemestrinus,  C.  callitrichus,  and  Papio 
babinm  were  susceptible;  Landsteiner  and  Levaditi  the  chimpanzee, 
M.  sinicus,  and  the  mandrill.  Flexner  and  Lewis  found  that  the 
monkeys  of  the  Xew  World  were  not  so  susceptible  as  those  of  the 
Old.  It  is  of  interest  to  note  that  phylogenetically  the  monkeys 
of  the  Xew  World  are  less  closely  related  to  man.  Liener  and 
v.  Vviesner  found  that  young  monkeys  were  more  susceptible  to 
the  disease  than  old  ones. 

(b)  THE  CLINICAL  HISTORY  OF  POLIOMYELITIS  IN 

MONKEYS. 

Period  of  Incubation. — I  have  personal  experience  only  of  cases 
which  were  caused  by  intracerebral  inoculation  or  simultaneous 
intracerebral  and  intraperitoneal  inoculation.  The  duration  of  the 
incubation  period  varied  from  three  and  a  half  days  to  fifteen  days, 


44  EPIDEMIC    INFANTILE   PARALYSIS 

an  average  of  nine  and  a  half  days.  Other  authors  record  a  similar 
average  figure.  The  shortest  period  observed  by  Landsteiner  and 
Levaditi  was  four  days,  the  longest  twenty.  Flexner  and  Lewis 
state  that  out  of  eighty-one  monkeys  eighteen  were  paralysed  before 
the  eighth  day,  and  sixteen  after  the  twelfth  day;  the  longest  period 
which  they  observed  was  thirty-three  days;  the  majority  of  the  ani- 
mals became  ill  between  the  eighth  and  twelfth  days.  Leiner  and 
v.  YVeisner  even  record  a  period  of  forty-six  days  in  one  case,  in 
which  the  virus  had  been  passed  through  a  Riechel  filter. 

The  amount  of  virus  used  seems  to  have  some  effect  upon  the 
length  of  the  incubation  period.  All  the  above  writers  report  that 
whenever  the  virus  was  passed  though  a  filter  capable  of  holding 
back  all  bacteria  the  incubation  period  was  longer.  It  is  probable 
that  the  filter  keeps  back  some  of  the  virus,  and  that,  in  effect,  a 
smaller  dose  of  virus  is  administered.  Leiner  and  v.  YYiesner  report 
a  case  in  which  the  spinal  cord  emulsion  was  first  centrifugalized,  then 
repeatedly  passed  through  filters  of  paper  and  wadding;  the  period  of 
incubation  with  the  filtered  virus  was  twenty-seven  days,  while  in  a 
control  in  which  unfiltered  virus  was  used  the  period  as  only  seven 
days.  Flexner  and  Lewis  have  observed  that  when  the  virus  is 
administered  by  any  other  way  than  by  intracerebral  injection  (e.g.f 
subcutaneously  or  into  the  peritoneum)  the  period  is  longer;  like- 
wise when  other  organs  than  the  brain  and  spinal  cord  are  used  for 
making  the  emulsion.  Leiner  and  v.  Wiesner  record  an  incubation 
period  of  twenty-three  days  in  a  monkey  which  had  been  given  the 
virus  by  mouth.  I  myself  gave  intracerebral  injections  of  the  con- 
centrated emulsion  to  two  monkeys,  one-tenth  of  the  dose  to  a 
third,  and  one-hundredth  of  the  dose  to  a  fourth:  the  first  two 
became  ill  on  the  seventh  day  and  died  on  the  eighth,  the  third 
sickened  on  the  twelfth  and  died  on  the  thirtieth  day.  while  the 
fourth  monkey  remained  well.  Leiner  and  v.  Wiesner  showed  that 
it  is  true  only  up  to  a  certain  point  that  an  increased  dose  shortens 
the  period  of  incubation  and  increases  the  severity  of  the  attack: 
when  a  certain  point  had  been  reached  they  found  that  increasing 
the  dose  made  the  incubation  longer  and  the  attack  less  severe. 
They  believe  that  the  central  nervous  system  contains  a  substance 
antagonistic  to  the  virus  (as  is  known  to  be  the  case  in  rabies), 
although  they  have  not  succeeded  in  demonstrating  its  presence  in 
monkeys. 

Prodromal  Symptoms. — Sometimes,  but  not  constantly,  certain 
indefinite  S)-mptoms  precede  the  paralysis.  The  monkeys  are  less 
merry;  they  are  tired,  do  not  climb  about  so  much;  their  expression 
becomes  discontented  and  surly;  sometimes  they  seem  to  age,  their 
eyes  become  dull.  Occasionally  there  is  a  tremor  of  the  whole 
body,  particularly  of  the  head.  Fairly  frequently  gastro-intestinal 
symptoms  appear,  anorexia,  diarrhoea,  and  sometimes  vomiting.  I 
have  observed,  however,  that  the  gastro-intestinal  symptoms  occur 
more  commonly  later  when  paralysis  is  beginning.  The  temperature 
did  not  show  any  characteristic  changes;  in  most  cases  our  animals 


ETIOLOGY   OF  THE   DISEASE 


45 


were  wild,  and  the  chase  necessary  to  capture  them  caused  a  con- 
siderable rise  in  temperature.  In  the  case  of  three  tame  animals  a 
reliable  record  could  be  obtained;  all  these  suffered  from  typical 
poliomyelitis  ending  in  death,  and  I  give  the  temperature  charts  in 
figs.  6  to  8.  Monkey  Xo.  4  shows  a  considerable  rise  of  tempera- 
ture two  days  before  any  paralysis  was  apparent;  on  the  first  day 
of  paralysis  the  temperature  remained  raised,  and  only  became 
subnormal  on  the  second  day  shortly  before  death.  In  monkeys 
Nos.  13  and  14  the  temperature  was  apparently  not  affected  by  the 
disease.  The  shaded  areas  in  the  figures  represent  the  degree  of 
paralysis.     Leiner  and  v.  Wiesner,   also  Flexner  and  Lewis,   could 


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not  find  any  typical  change  in  temperature   during  the  prodromal 
sta°"e. 

Vtage  Of  Paralysis..— This  stage  frequently  begins  suddenly 
without  any  warning  symptoms.  Monkeys  which  in  the  evening 
were  seen  to  be  quite  lively  were  found  paralysed  in  one  or  more 
limbs  on  the  following  morning;  even  during  the  day  in  the  course  of 
a  single  hour  a  monkey  became  severely  paralysed.  The  clinical 
course  varied  very  much  in  different  animals.  The  several  types  of 
paralysis,  together  with  the  examples  on  which  they  are  based,  will 
be  described  below.  Of  great  interest  and  importance  from  the  point 
of  view  of  the  pathogenesis  of  the  disease  is  the  fact  that,  although 


46 


EPIDEMIC   INFANTILE   PARALYSIS 


the  monkeys  were  infected  in  the  brain,  the  paralysis  is  in  almost 
all  cases  of  the  spinal  type,  flaccid  and  with  consequent  atrophy, 
while  the  paralysis  affects  the  limbs  first  of  all;  further,  the  lower 
limbs  are  affected  more  often  and  more  severely  than  the  upper. 
The  type  of  paralysis  which  is  most  common  in  man  is  most  common 
in  monkeys.  There  is  therefore  a  close  analogy  between  the  disease 
artificially  produced  in  monkeys  and  that  occurring  naturally  in 
man,  although  the  point  of  entrance  of  the  virus  is  undoubtedly 
different  in  the  two  cases. 


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Fig  8. 
Monkey  No.    14. 

(a)  Poliomyelitis  acutiSSima.—  After  intracerebral  infection  the 
course  of  the  disease  may  be  so  rapid  that  one  can  hardly  speak  of 
a  paralytic  stage.     The  following  are  two  such  cases:  — 

Monkey  No.  45  {Macacits  rhesus)  was  injected  on  Apiil  7,  19 10,  with 
"5  c.c.  of  emulsion  of  virus  No.  6,  and  at  the  same  time  with  4  c.c.  of  the 
same  intraperitoneally. 

At  10  o'clock  on  the  evening  of  the  13th  eyes  dim;  climbs  about  in  a 
tired  way,  but  with  complete  control  of  all  limbs. 

At  7  a.m.  on  the  14th  found  dead  in  the  cage. 

On  histological  examination,  typical  changes  in  cord  and  medulla. 


Monkey  No.    1    [Cercofithecus  fuliginosus),  intracerebral  injection   with 
'5  c.c.  of  virus  No.  6  on  September  6,  igog. 
September  7-12. — No  change. 
September    13. — Languid    and    sad;    no    paresis   visible.     At    n    p  m.    I 


ETIOLOGY  OF  THE  DISEASE  47 

happened  to  be  at  the  laboratory,  and  observed  a  slight  paresis  of  the  left 
fore  limb;  the  animal  still  used  the  limb,  but  it  gave  way  under  him,  and 
there  was  less  resistance  to  passive  movements.  The  tone  of  the  muscles 
appeared  diminished. 

September  14. — The  monkey  lies  on  the  floor  apparently  completely 
paralysed  in  all  limbs.  The  mind  is  clear;  with  the  eyes  he  follows  move- 
ments of  objects.  The  neck  muscles  appear  unaffected.  On  trying  to  place 
him  on  his  feet  he  collapses  at  once.  Death  occurred  in  the  evening.  The 
-post  mortem  revealed  very  typical  poliomyelitis. 

In  both  these  animals  (Nos.  45  and  1)  the  form  of  the  disease 
was  so  acute  and  atypical  that  it  would  have  been  difficult  to  be 
certain  that  death  was  due  to  infection  with  poliomyelitis  if  it  were 
not  for  the  microscopical  examination  and  the  results  of  inoculating 
the  virus  into  fresh  animals.  In  the  most  severe  cases,  where  all 
four  limbs  are  affected  together  and  suddenly,  it  is  difficult  to 
determine  whether  the  animal  is  suffering  merely  from  extreme 
general  weakness  due  to  a  severe  infectious  disease  or  from  an 
actual  paralysis  due  to  a  lesion  in  the  spinal  cord.  Leiner  and 
v.  Wiesner  also  record  a  case  in  which  death  occurred  without  any 
preliminary  paralysis  on  the  sixth  day  after  infection;  in  this  case 
the  cause  of  death  was  proved  to  be  true  poliomyelitis  by  means  of 
microscopical  examination.  Flexner  and  Lewis  also  report  a  case 
of  experimental  poliomyelitis  in  a  monkey  in  which  death  occurred 
a  few  hours  after  the  onset  of  paralysis.  Such  cases  remind  one 
of  Landry's  disease  in  man;  Wickman  finds  that  the  great  majority 
of  cases  of  Landry's  disease  are  merely  examples  of  a  particular 
type  of  Heine-Medin  disease. 

(b)  Poliomyelitis  acuta. — In  other  cases  death  does  not  occur 
so  rapidly,  but  still  more  quickly  than  in  the  majority  of  human 
cases.     An  example  is  the  following:  — 

Monkey  Xo.  2  [Cercofithecits  fuligiiiosus). — On  November  17,  1909, 
received  an  intracerebral  injection  of  '4  c.c.  of  an  emulsion  made  from 
virus  No.  6. 

November  17-26. — Remained  well. 

November  27. — Depressed;  remains  huddled  on  the  floor  of  his  cage. 
No  apparent  paralysis. 

November  28. — Marked  flaccid  palsy  of  both  hind  limbs ;  moderate  degree 
of  flaccid  palsy  of  fore  limbs ;  the  hind  limbs  can  still  be  moved  with  the 
help  of  the  fore  limbs ;  movements  of  the  tail  still  powerful ;  the  muscles 
of  the  back  seem  to  be  affected.  No  cranial  nerve  lesions.  Death  during 
the  night  of  November  28. 

The  histological  findings  were  very  typical. 

(c)  Typical  Spinal  Paralysis. — Other  cases  are  quite  comparable 
to  those  in  man.  which  develop  gradually,  show  wide  spread  of  the 
paralysis,  and  end  in  death  within  a  few  days.     Examples  are:  — 

Monkey  No.  29  {Macacas  rhesus)  received  an  intracerebral  injection  on 
February  7,  1910,  '35  c.c.  of  virus  No.  12,  filtered  through  paper  and  mixed 
with  '35  c.c.  of  the  serum  of  a  healthy  monkey. 


48  EPIDEMIC   INFANTILE   PARALYSIS 

February  8-14. — Remained  well. 

February  15. — When  walking  in  the  evening  spares  the  right  hind  limb. 

February  16. — Both  hind  limbs  almost  entirely  paralysed;  upper  limbs 
appear  quite  unaffected.  The  monkey  moves  forwards  by  means  of  the 
arms  and  drags  the  flaccid  hind  limbs. 

February  17. — Total  flaccid  palsy  of  the  hind  limbs. 

February  18,  a.m.,  in  statu  quo  ante;  p.m.,  the  resistance  of  the  right 
fore  limb  is  less  on  passive  movement;  the  limb  frequently  gives  way  under 
the  animal.     Much  diarrhoea. 

February   iq. — Condition  unchanged. 

February  20. — In  statu  quo.     Diarrhoea  has  ceased. 

February  21. — The  fore  limbs  are  now  completely  paralysed;  the 
monkey  lies  quite  flaccid  on  the  ground ;  apparently  the  muscles  of  the  neck 
are  paralysed,  as  the  chin  also  lies  on  the  ground;  there  is  no  resistance  to 
passive  movement  of  the  head,  and  it  drops  on  to  the  ground  when  one  lets 
go  of  it.      Xo  lesion  of  the  cerebral  nerves. 

February  22. — Death. 

Histological  examination  shows  typical  poliomyelitis,  mainly  in  the 
lumbar  cord  and  the  medulla. 


FIG.   9. 
Monkey  No.    14. 

Monkey  Xo.  14  [Macacus  rhesus),  intracerebral  injection  of  '5  c.c.  of 
virus  Xo.   11  emulsion  on  December  17,   iqoq. 

December  18-25. — Xo  signs  of  illness. 

December  26. — Slight  weakness  of  the  hind  limbs,  which  often  give  way 
under  the  animal  and  cause  it  to  fall  to  one  side.  Otherwise  they  can  be 
nsed  quite  well.      The  resistance  of  the  hind  limbs  seems  less  than  normal. 

December  27. — Almost  total  flaccid  palsy  of  the  hind  limbs. 

December  28. — Fore  limbs  now  markedly  paralysed.  Resistance  to  pas- 
sive movements  still  quite  good  in  the  fore  limbs. 

December  2Q. — Total  flaccid  palsy  of  all  limbs.  Cranial  nerves  not 
affected ;  compare  the  photograph  above,  which  was  taken  on  this  day. 

December  30. — Death  at  2  p.m. 

Microscopic  appearances  in  the  cord  are  typical. 


Monkey  Xo.  46  {Macacus  rhesus),  intracerebral  injection  of  '5  c.c.  and 
intraperitoneal  injection  of  4  c.c.  of  an  emulsion  of  virus  Xo.  11  on  April  7, 
1910. 


ETIOLOGY   OF  THE   DISEASE  49 

April  8-16. — Xo  apparent  disturbance. 

April  17. — Marked  flaccid  pals}-  of  the  right  hind  limb.  Much  diarrhoea. 
In  the  afternoon  total  paralysis  of  the  right  and  possibly  a  slight  palsy  of 
the  left  hind  limb. 

April  18. — In  the  morning  total  paralysis  of  both  hind  limbs.  The 
monkey  can  move  only  by  means  of  the  fore  limbs.  On  attempting  to  climb 
he  pulls  himself  up  by  his  fore  limbs,  but  is  unable  to  use  his  hind  limbs. 
In  the  evening  found  crouching  on  the  floor  of  his  cage.  Marked  palsy 
of  the  right  upper  limb.  Can  no  longer  climb  at  all ;  the  animal  cannot 
even  climb  over  the  threshold  of  the  cage,  which  is  only  15  cm.  high.  He 
can  still  seize  and  grasp  an  apple  with  the  left  hand. 

April  ig. — Condition  in  statu  quo.     Slight  palsy  of  left  arm. 

April  20. — Total  flaccid  palsy  of  all  extremities. 

April  21. — Moribund.     Death  during  the  afternoon. 

Histological  examination. — Very  typical  changes  of  poliomyelitis  in 
the  spinal  cord. 

(d)  Bulbar  and  Cerebral  Forms. — The  preceding  types  are  the 
most  common  in  monkeys;  they  are  spinal  only  in  so  far  as  clinical 
observation  is  concerned,  as  the  microscopical  appearances  always 
show  more  widespread  disease  than  one  would  expect  from  the 
clinical  signs.  In  most  of  my  cases  the  paralysis  was  of  the  ascend- 
ing type,  beginning  in  the  leg's,  next  attacking  the  arms,  and  finally 
causing"  death  by  involvement  of  the  medulla.  I  lay  particular 
stress  on  this  point  because  the  path  of  infection  was  in  all  cases  by 
the  brain  and  in  most  cases  exclusively.  I  shall  return  to  this  later. 
Occasionally  the  cerebral  nerves  were  affected,  and  in  most  of  such 
cases  it  was  possible  to  demonstrate  that  the  nerve  nuclei  were 
affected  by  the  disease.  These  cases  constitute  therefore  a  bulbar 
type  quite  similar  to  that  observed  in  man. 

Monkey  Xo.  48  [Macacus  rhesus),  on  April  7,  iqio,  received  an  intra- 
cerebral injection  of  '5  c.c.  and  an  intraperitoneal  injection  of  4  c.c.  of  an 
emulsion  of  virus  X"o.   11. 

April  8-16. — Xo  signs  of  disease. 

April  17. — Slight  palsy  of  the  left  fore  limb  and  the  right  hind  limb 
just  perceptible.  AVhen  climbing  about  his  cage  the  monkey  falls  frequently. 
In  the  afternoon  the  left  arm  quite  paralysed;  the  palsy  of  the  right  leg 
more  marked. 

April  18. — Besides  the  paralysis  of  the  left  arm  there  is  some  paralysis 
of  both  hind  limbs.  In  the  evening  weakness  of  the  right  arm.  The  animal 
falls  to  one  side  while  walking. 

April  ig. — The  monkey  sits  crouching  on  the  floor  of  the  cage.  Total 
palsy  of  the  left  arm,  definite  weakness  of  the  right  arm.  The  animal  is 
still  able  to  hold  a  small  apple  in  the  right  hand  for  some  minutes.  Marked 
palsy  of  both  hind  limbs.  AVhile  walking  the  monkey  falls  sometimes  to 
one  side  and  sometimes  forward.  The  head  hangs  forward  owing  to 
paralysis  of  the  muscles  of  the  neck.  Movements  of  the  tail  are  strong. 
There  is  also  a  marked  palsy  of  the  lower  part  of  the  left  facial  nerve, 
which  is  very  obvious  when  the  monkey  is  made  to  express  pain.  The  left 
angle  of  the  mouth  is  not  moved,  nor  does  the  lower  part  of  the  left  cheek 
show  any  trace  of  the  wrinkling  which  is  seen  on  the  right  side.  In  the 
evening  the  monkey  became  moribund  and  was  killed. 

4 


5o 


EPIDEMIC   INFANTILE   PARALYSIS 


Unfortunately  it  was  not  possible  to  obtain  a  photograph  of  the  facial 
paralysis,  because  the  animal  was  so  ill  that  the  expression  of  pain  was  only 
momentary.  Professor  Miiller  succeeded  in  the  case  of  another  monkey  in 
photographing  a  facial  palsy,  and  with  his  permission  I  have  reproduced 
his  photograph  of  a  total  right-sided  paralysis. 

Leiner  and  v.  Wiesner  have  also  observed  facial  palsy. 
Levaditi  and  Stanesco  have  described  a  very  beautiful  case  of  which 
they  obtained  a  characteristic  photograph  (cf.  fig.  n).  The 
paralysis  of  the  whole  of  the  left  facial  nerve  set  in  on  the  ninth 
day  after  an  intracerebral   injection;   the  muscles  of  the   eye   were 


Fig.   io. 

Monkey  No.   102. 

Right-sided  facial  paralysis. 


likewise  affected.  The  case  is  remarkable  in  that  the  facial  palsy 
was  the  first  sign  of  the  disease  noticed,  the  paralysis  of  the  limbs 
following  later. 

Levaditi  and  Stanesco  found  marked  changes  in  the  ganglion 
cells  of  the  facial  nerve. 

Netter,  as  well  as  Flexner  and  Lewis,  observed  facial  paralysis. 
Flexner  and  Lewis  give  one  illustration  of  the  condition;  the  photo- 
graph also  shows  a  definite  paralysis  of  the  hypoglossal  nerve,  the 
tongue  deviates  to  the  left,  on  which  side  the  facial  nerve  was 
paralysed  (fig.  12). 


ETIOLOGY   OF  THE   DISEASE 


SI 


Fig.  n. 
Left-sided  facial  paralysis.      (After  Levaditi  and  Stanesco.) 


FIG.    12. 

Paralysis  of  the  facial  and  hypoglossal  nerves  on  the  left  side. 
(After  Flexner  and  Lewis.) 


52 


EPIDEMIC   INFANTILE   PARALYSIS 


Monkey  No  61  {Macacus  rhesus)  received  on  June  3,  igio,  an  intra- 
cerebral injection  of  '6  c.c.  of  a  5  per  cent,  emulsion  of  virus  No.  11  (mixed 
with  normal  human  serum). 

June  14-17. — No  signs. 

June  18. — Slight  paresis  of  the  right  fore  limb.  During  the  afternoon 
this  became  more  marked  and  was  definitely  flaccid  in  type.  The  hind 
limbs  were,  on  the  other  hand,  very  markedly  spastic  ;  the  animal  frequently 
fell  down  when  the  hind  limbs  showed  a  strong  tremor.  In  addition  there 
was  a  marked  ptosis  on  the  right  side,  the  eyeball  was  deviated  outwards 
and  downwards  and  could  not  be  made  parallel  to  the  left  eyeball.  No 
changes  were  observed  in  the  pupils  (fig.  13). 


IWHP 


Fig.   13. 

Monkey  No.  61. 

Paralysis  of  the  right  oculomotor  nerve. 

June  iq. — Found  dead. 

On  microscopical  examination  considerable  lesions  were  found  in  the 
cerebral  cortex  and  in  the  basal  ganglia.  The  changes  in  the  cord  were 
less  marked. 

In  this  case  the  oculomotor  nerve  was  affected,  and  at  the 
same  time  the  limbs  were  involved  owing  both  to  cerebral  and  spinal 
lesions. 


ETIOLOGY  OF  THE  DISEASE  53 

Other  cases  were  observed  in  which  the  disease  was  even  more 
definitely  cerebral  in  type;  cases  analogous  to  the  cerebral  type  of 
Heine-Medin  disease  in  man. 

Monkey  No.  27  (Mangabey)  received  on  March  3,  1910,  an  intracerebral 
injection  of  '6  c.c.  of  an  emulsion  of  virus  Xo.   12. 

March  3-10. — Remained  well. 

March  11. — Depressed. 

March  12. — Clearly  ill,  breathing  heavily. 

March  13. — Frequent  tremor  of  the  whole  body.  Walks  stiffly  and  with 
difficulty,  but  is  not  definitely  paralysed. 

March  14. — Lies  on  the  floor;  extremities  show  violent  tremors  and  are 
stiff.     Died  at  4  p.m. 

On  microscopical  examination  typical  poliomyelitis.  The  changes  affect 
the  pia  mater  in  the  region  of  the  central  gyri ;  much  perivascular  infiltra- 
tion in  the  cerebral  cortex  and  in  the  basal  ganglia.  Very  slight,  apparently 
only  beginning,  changes  in  the  spinal  cord. 

Relatively  seldom  therefore  a  purely  cerebral  form  of  experi- 
mental poliomyelitis  occurs  in  monkeys.  Flexner  and  Lewis  record 
similar  cases  in  which,  however,  convulsions  occurred,  a  thing  I 
never  observed.  Flexner  found  in  eight  out  of  eighty-one  cases 
that  the  disease  began  with  cerebral  or  bulbar  symptoms,  although 
these  cases  became  later  spinal  in  type.  In  one  monkey  in  which 
the  paralysis  was  due  chiefly  to  the  cerebral  lesions  they  observed 
distinct  nystagmus ;  this  is  the  only  time  that  nystagmus  has  been 
observed  in  a  monkey  so  far  as  I  know. 

The  symptom-complex  due  to  cerebral  localization  of  the  lesion 
of  poliomyelitis  in  monkeys  is  by  no  means  characteristic;  in  any 
case  caution  is  necessary  in  making  the  diagnosis  of  a  purely  cere- 
bral lesion  from  the  symptomatology  alone  in  experimental  polio- 
myelitis; unless  the  diagnosis  is  controlled  by  microscopical 
examination  mistakes  may  easily  occur.  The  following  cases  illus- 
trate this  point :  — 

Monkey  Xo.  7  [Macacus  rhesus)  inoculated  on  December  17,  1909,  with 
■5  c.c.  of  an  emulsion  of  virus  Xo.  11. 

December  19. — Marked  spastic  paresis  of  the  right  hind  limb  and 
moderate  spastic  paresis  of  the  right  fore  limb. 

December  20. — Condition  the  same. 

December  21. — Paresis  apparently  less  marked. 

December  22. — Paralysis  increased,  the  degree  varies  during  the  day. 

December  23. — Found  dead. 

On  examination  none  of  the  lesions  typical  of  Heine-Medin  disease  were 
found  in  the  cerebral  cortex  or  elsewhere.  The  paralysis  was  due  to  an 
abscess,  the  size  of  a  hazel-nut,  in  the  region  of  the  central  gyri  on  the 
left  side  at  the  site  of  the  injection.  From  this  abscess  streptococci  were 
cultivated. 


Monkey   Xo.    60    [Macacus    rhesus)    inoculated    on    July    13,    1910,    with 
■5  c.c.  of  emulsion  of  virus  Xo.  11. 

July  15. — Unsteady  while  jumping. 

July  16. — Definite  weakness  of  both  left  limbs. 


54  EPIDEMIC   INFANTILE   PARALYSIS 

July  17-25. — Very  marked  paresis  of  the  left  fore  limb,  of  a  spastic 
kind. 

July  26-28. — Paralysis  increasing. 

July  29. — Found  dead. 

Microscopically  no  lesions  indicative  of  poliomyelitis  were  found.  In 
the  right  central  gyri  at  the  point  of  inoculation  an  abscess  the  size  of  a 
bean. 

(e)  Castro-intestinal  Symptoms. — Diarrhoea  coincident  with 
the  paralysis  has  already  been  mentioned  above,  and  in  some  of  the" 
cases  reported.  It  is  difficult  to  decide  whether  the  poliomyelitis 
is  the  cause  of  the  diarrhoea  because  so  many  monkeys,  when 
bought  recently,  suffer  from  gastro-intestinal  disturbance  owing  to 
change  of  surroundings  or  of  food.  At  the  same  time,  the  number 
of  cases  in  which  diarrhoea  occurred  at  the  same  time  as  paralysis  is 
so  large,  even  in  monkeys  which  had  been  kept  in  the  institution  for 
a  considerable  time,  that  I  have  no  doubt  that  the  gastro-intestinal 
symptoms  are  a  part  of  the  poliomyelitic  infection.  The  following 
are  examples  :  — 

Monkey  Xo.  23  {Macacus  rhesus)  inoculated  on  January  20,  1910; 
'5  c.c.  into  the  brain  and  5  c.c.  into  the  peritoneum. 

January  21-26. — No  symptoms. 

January  26. — In  the  evening  the  monkey  seems  more  tired  than  usual. 

January  27. — Sudden  violent  diarrhoea;  at  the  same  time  total  flaccid 
paralysis  of  the  hind  limbs  with  slight  paresis  of  the  fore  limbs. 

January  28. — Diarrhoea  has  ceased.  Paralysis  of  the  hind  limbs  the 
same,  of  the  fore  limbs  more  marked.      Paralysis  of  the  bladder. 

January  29. — Complete  paralysis  of  all  limbs.  Death  during  the  after- 
noon. 

Microscopic  appearances  in  the  cord  are  typical. 


Monkey  Xo.  38  [Macacus  rhesus). — Intracerebral  inoculation  on  March 
2,  1910,  with  '35  c.c.  of  an  emulsion  of  virus  Xo.  12  (mixed  with  serum  from 
a  normal  monkey). 

March  3-9. — No  symptoms. 

March  10. — 111;  takes  food  badly;  severe  diarrhoea;  no  paralysis. 

March  11. — General  condition  the  same.  Unsteady  gait.  Resistance  to 
passive  movement  is  diminished  in  all  limbs.  Xo  definite  paralysis  observed 
when  walking. 

March  12. — Monkey  lies  apparently  completely  paralysed  on  the  floor 
of  the  cage.     Death  12  noon. 

At  the  fost-mortem  there  was  found  severe  gastro-enteritis  with  redness 
and  swelling  of  the  follicles  of  the  small  intestine  and  of  Peyers  patches ; 
the  mesenteric  glands  were  increased  in  size,  being  as  large  as  beans. 
Typical,  but  not  intense,  changes  in  the  brain  and  spinal  cord.  Cultures 
made  from  the  blood  and  from  the  glands  remain  sterile.  (Intracerebral 
injection  of  material  from  the  mesenteric  glands  into,  another  monkey  pro- 
duced typical  poliomyelitis,  cf.  p.  98). 

(f)  Abortive  Forms. — Wickman  did  great  service  in  calling 
attention  to  cases  of  Heine-Medin  disease  in  man. in  which  there 
are  no  definite  symptoms  of  paralysis;  he  named  this  the  abortive 


ETIOLOGY   OF   THE   DISEASE 


;>o 


type.  In  monkeys  it  is  possible  to  produce  a  slight  as  well  as  a 
severe  form  of  the  disease.  It  is  difficult  to  decide  whether  true 
abortive  forms  without  paralysis  occur  in  monkeys,  because  we  have 
no  criteria  by  which  we  can  determine  the  causal  connection 
between  the  general  malaise  and  the  injection  of  the  virus.  It  may 
be  possible  later  to  furnish  proof  by  means  of  serum  diagnostic 
tests  (vide  infra).  Personally  I  have  no  doubt  at  the  present  time 
that  such  cases  occur,  because  of  the  very  slight  and  transient 
palsies  which  I  have  observed.  The  following  two  examples  may 
be  considered  within  certain  limits  to  be  cases  of  "  abortive  " 
experimental  poliomyelitis. 


Fig.   14. 

Monkey  No.  44. 

A  trace  of  paralysis  of  the  right  hind  limb. 


Monkey  No.  44  {Macacus  rhesus),  on  March  23,  1910,  intracerebral 
injection  of  '6  c.c.  of  an  emulsion  of  virus,  also  3  c.c.  into  the  peritoneum. 

March  23-28. — No  symptoms. 

March  29. — The  monkey  appears  more  tired  than  usual. 

March  30. — Severe  diarrhoea.  "Weakness  of  the  right  hind  limb, 
scarcely  noticeable  on  walking,  but  obvious  when  the  animal  is  sitting ; 
the  right  leg  cannot  be  adducted  as  strongly  as  the  left.  "Wherever  one 
places  the  monkey  it  always  assumes  this  peculiar  attitude,  which  is  shown 
well  in  the  photograph  (fig.   14). 

March  31. — Diarrhoea  less.     Paralysis  almost  disappeared. 

April  1  and  subsequently. — Quite  normal. 


56  EPIDEMIC  INFANTILE  PARALYSIS 

Monkey  Xo.  59  [Macacus  rhesus). — Intracerebral  injection  on  June  13, 
igio,  with  '3  c.c.  of  emulsion  of  virus  Xo.  11  (mixed  with  normal  human 
serum). 

June  15-21. — Xo  symptoms. 

June  22. — Severe  diarrhoea. 

June  23. — Condition  the  same. 

June  24. — Similar  condition;  in  addition,  slight  paresis  of  the  right 
fore-limb. 

June  25. — Unchanged. 

June  26. — Paresis  almost  absent;  diarrhoea  less. 

June  27. — Complete  recovery. 

That  in  this  case  the  virus  was  responsible  for  the  condition  was  proved 
later.  On  reinoculation  this  animal  remained  well  while  the  control  died 
[cf.  p.   153). 

Such  abortive  cases  appear  to  be  rare  in  monkeys.  This  may 
be  owing  to  the  slighter  symptoms  being  missed;  even  paralysis 
can  be  observed  with  certainty  only  when  it  is  fairly  well  marked. 
In  the  last  cases  quoted  above  the  paralysis  was  noticed  because  we 
had  already  considerable  clinical  experience.  Flexner  and  Lewis 
have  no  doubt  of  the  existence  of  abortive  forms  of  experimental 
poliomyelitis  in  monkeys. 

In  some  cases  I  observed  general  weakness,  the  monkeys 
looked  ill  and  suffered  from  gastro-intestinal  symptoms,  but  as  no 
paralysis  occurred  it  was  not  possible  to  associate  the  symptoms 
directly  with  the  infection.  I  intended  to  test  the  immunity  of  these 
animals  by  repeating  the  injection,  but  they  died  shortly  afterwards 
from  tuberculosis  of  the  lungs.  In  my  statistics  I  have  included 
them  among  the  unsuccessful  inoculations. 

(g)  Marasmic  Forms. — Leiner  and  v.  Wiesner  described  this 
form,  but  I  have  not  had  any  opportunity  of  observing  it.  These' 
authors  describe  it  as  follows:  "After  inoculation  the  animals 
remained  for  some  time  well;  towards  the  end  of  the  incubation 
period  they  became  depressed,  tired,  suffered  from  diarrhoea  (which 
cleared  up  under  treatment),  wasted  rapidly,  did  not  care  to  move 
about,  were  able  to  climb  but  did  not  wish  to  do  so,  the  muscular 
power  was  generally  diminished;  in  one  word,  they  became 
marasmic.  Some  of  them  died  between  the  sixth  and  thirteenth  day 
after  inoculation  without  showing  any  signs  of  paralysis,  others 
lingered  on  for  a  longer  time.  Microscopical  examination  showed 
beyond  the  possibility  of  doubt  that  these  animals  were  suffering 
from  an  atypical  form  of  poliomyelitis.  Besides  hyperemia  and 
haemorrhages  there  was  marked  degeneration  of  the  ganglion  cells 
with  a  certain  amount  of  cell  infiltration.  We  are  convinced  that 
these  animals  succumbed  to  an  atypical  form  of  poliomyelitis  with- 
out paralysis.  The  striking  feature  of  this  form  is  the  wasting  of 
the  animals,  and  we  have  called  it  therefore  the  '  marasmic  '  type." 
Leiner  and  v.  Wiesner  have  produced  confirmatory  evidence  of  their 
contention  by  inoculating  other  monkeys  with  the  spinal  cord  of 
these,    and  finding   that    the    new    monkeys    died    of    typical    polio- 


ETIOLOGY   OF  THE   DISEASE  57 

myelitis.  Eduard  Miiller  reports  a  human  case  in  which  he  observed 
marked  general  wasting  although  ample  nourishment  was  taken. 
He  compares  his  case  with  those  reported  by  the  Austrian 
observers. 

(h)  Recovery  from  the  Acute  Stage. — The  foregoing  types  are 
all  characterized  by  the  fact  that  almost  all  the  monkeys  succumbed 
to  the  disease.  In  man  it  is  more  usual  for  life  to  be  preserved, 
even  though  the  extent  of  the  paralysis  is  considerable.  In 
monkeys  such  cases  are  rare;  in  my  small  amount  of  material  I 
saw  one  such  case:-  — 

Monkey  Xo.  37  (Macacus  rhesus). — Intracerebral  injection  on  March  2, 
1910,  with  '3  c.c.  of  an  emulsion  of  virus  Xo.  12  (mixed  with  the  serum  of 
a  normal  monkey). 

March  3-8.— Healthy. 

March  g. — Marked  weakness  of  the  right  hind  limb ;  left  somewhat 
weak. 

March  10. — Flaccid  paralysis  of  both  hind  limbs;  severe  diarrhcea. 

March  n. — Complete  paraplegia. 

March  12  and  the  weeks  following. — The  condition  remained  the  same; 
there  was  total  flaccid  paralysis  of  the  hind  limbs,  while  the  rest  of  the 
muscles  acted  well.  On  walking  the  hind  limbs  are  dragged.  Climbing 
must  be  carried  out  by  the  arms  alone  and  the  monkey  therefore  soon 
becomes  tired.  The  monkey  was  cinematographed  in  this  condition,  and  the 
film  was  shown  at  the  Congress  for  Internal  Medicine  at  Wiesbaden  in 
April,  1910.  Occasionally  oedema  of  the  legs  was  observed.  This  can  be 
explained  by  the  position  assumed  by  the  monkey  when  sitting  on  its 
board,  the  hind  limbs  hung  down  over  the  edge  and  the  consequent  com- 
pression of  the  vessels  caused  the  oedema.  At  the  same  time  one  must  bear 
in  mind  the  possibility  of  vasomotor  paralysis  as  a  factor.  The  monkey 
died  on  April  14  in  a  marasmic  condition. 

(i)  Recovery  from  the   Paralysis. — In   other  cases,   as  is   so 

common  in  man,  we  observed  considerable  improvement  in  the 
paralysis. 

Monkey  Xo.  47  (Macacus  rhesus). — On  April  7,  1910,  intracerebral 
injection  of  '5  c.c.  of  emulsion  of  virus  Xo.  11,  also  4  c.c.  into  the  peri- 
toneum. 

April  8-16. — Xo  change. 

April  17. — Slight  weakness  of  left  hind  limb.  Falls  frecpuently  while 
climbing.      In  the  afternoon  paresis  of  both  hind  limbs. 

April  18. — Marked  flaccid  paralysis  of  both  hind  limbs.  The  monkey 
uses  the  arms  only  while  climbing. 

April  19-21. — Practically  the  same.  The  monkey  walks  with  the  arms 
only,  dragging  the  legs,  which  are  completely  flaccid. 

April  22. — Condition  the  same;  incontinence  of  urine. 

April  26. — The  left  hind  limb  is  used  slightly;  the  right  hind  limb 
appears  cedematous  at  times. 

May  2. — The  paralysis  of  the  left  hind  limb  is  much  less  and  can  be 
observed  only  by  testing  the  resistance  of  the  limb  to  passive  movements. 

May  21. — Xo  paralysis  of  the  left  hind  limb;  the  right  hind  limb  is  still 
completely  paralysed.     The  photograph  represents  the  monkey  at  this  stage; 


58 


EPIDEMIC   INFANTILE   PARALYSIS 


the  total  paralysis  of  the   right  leg   can  be   seen  clearly   on   comparing  the 
attitude  of  the  limb  with  that  of  the  left  leg  which  is  normal   (fig.    15). 

Complete  recovery  from  severe  and  extensive  paralysis  was 
seen  in  the  following  cases  :  — 

Monkey  No.  32  {Macacus  rhesus)  on  February  7,  19 10,  received  an  intra- 
cerebral injection  of  '5  c.c.  of  an  emulsion  of  virus  No.  12  which  had  been 
warmed  for  half  an  hour  at  a  temperature  of  450  C. 

February  8-14. — Quite  well. 

February   15. — Slight  palsy  of  both  hind  limbs. 

February  16. — Paralysis  more  marked. 

February   17-20. — Condition  unchanged. 

February  21. — The  paralysis  is  less;  improvement  more  marked  in  the 
right  than  in  the  left  limb. 

February  26. — Only  a  trace  of  weakness  remains  in  the  left  hind  limb. 

March  12  onwards. — The  monkey  remained  quite  well. 


Fig.  15. 

Monkey  No.  47. 

Paralysis  of  the   left  hind   limb. 


Monkey  No.  40  {Macacus  rhesus). — On  March  4,  1910, 
injection  of  '6  c.c.  of  an  emulsion  of  virus  No.  12,  also  4 
peritoneum. 

March  5-10. — No  symptoms. 

March  12. — Slight  paralysis  of  both  hind  limbs.  - 

March  14. — Paralysis  of  both  limbs  well  marked. 

March  15-23. — Condition  unchanged. 

March  24. — Definite  improvement  in  paralysis. 

March  25  onwards. — The  improvement  is  rapid. 

April  3. — Paralysis  entirely  disappeared. 


intracerebral 
c.c.    into   the 


ETIOLOGY   OF  THE   DISEASE  59 

Monkey  No.  41  {Macacus  cynomolgus). — Intracerebral  injection  of 
'6  c.c.  of  virus  Xo.   11  on  March  15,  19 10. 

March  16-25. — No  change. 

March  26. — Slight  paresis  of  hind  limbs. 

March  27. — Unchanged. 

March  28. — Paresis  of  hind  limbs  more  marked;  definite  slight  paresis 
of  the  right  fore  limb. 

April  1. — Condition  of  hind  limbs  improved;  the  right  fore  limb  now 
total  flaccid  paralysis. 

April  5  onwards. — Steady  improvement  in  all  the  affected  limbs. 

May  5. — No  paralysis  in  any  limb. 


Monkey  No.  40  [Macacus  rhesus)  received  an  intracerebral  injection  ot 
'6  c.c.  of  an  emulsion  of  virus  No.   12  on  April  27,  1910. 

April  28  to  May  9. — No  symptoms. 

May  10. — Paresis  of  hind  limbs,  right  more  than  left. 

May  11-12. — No  change. 

May  13. — Paresis  less,  barely  perceptible  on  left  side. 

May  14-15. — No  change. 

May  16. — Monkey  climbs  well ;  there  is  still  a  slight  weakness  of  the 
left  limb. 

May  21. — No  paralysis  at  all. 

(k)  Relapses. — One  case  may  be  quoted  as  a  curiosity  in  which 
there  was  a  definite  relapse ;  the  monkey  appeared  undoubtedly 
to  be  recovering.  Such  a  sequence  of  events  is  sometimes  found 
in  human  poliomyelitis. 

Monkey  No.  11  (Macacus  rhesus). — Intracerebral  injection  of  '5  c.c.  of 
an  emulsion  of  virus  No.   11  on  December  8,   1909. 

December  9-19. — No  symptoms. 

December  20. — Severe  paralysis  of  right  hind  limb;  perhaps  also  a 
slight  paresis  of  the  arms. 

December  21. — Marked  paralysis  of  both  hind  limbs;  slight  paresis  of 
the  arms. 

December  22-25. — No  change. 

December  28  onwards. — Much  improvement  in  all  limbs;  paresis  in  the 
arms  scarcely  noticeable.  The  hind  limbs  are  used  occasionally.  The 
improvement  is  considerable. 

January  g. — Monkey  becomes  suddenly  weaker. 

January  10. — Hind  limbs  almost  completely  paralysed ;  the  animal  drags 
them  after  it.  In  the  evening  the  fore  limbs  appear  completely  paralysed 
and  the  monkey  lies  flat  on  the  floor  of  the  cage. 

January   11. — Found  dead. 

Microscopical  exmination  shows  typical  acute  changes  in  the  spinal 
cord. 

Levaditi  and  Stanesco  report  a  similar  case.  In  a  monkey 
which  became  paralysed  on  the  eleventh  day  after  injection  and 
died  on  the  twenty-ninth  day  in  a  condition  of  chronic  paralysis, 
they  found   both   acute   and   chronic   lesions   in   the   spinal   cord. 

It  is  extremely  difficult  to  say  whether  any  disturbance  of 
sensation    occurs    in    monkevs.     Absolute    and    relative    anaesthesia 


60  EPIDEMIC   INFANTILE   PARALYSIS 

cannot  be  tested  for  with  any  certainty.  It  appears  to  me,  however, 
that  shortly  before  the  paralysis  appears  there  is  a  stage  of  hyper- 
sesthesia  similar  to  that  observed  in  man  on  which  Eduard  Miiller 
lays  so  much  diagnostic  stress.  Monkeys,  which  previously  had 
been  quiet  and  friendly,  uttered  loud  cries  when  they  were  touched 
or  when  the  attempt  to   capture  them  made   them  move   about. 

It  is  quite  certain,  from  our  purely  clinical  observations,  that 
in  monkeys  the  spinal  symptoms  of  the  disease  are  the  most 
marked,  whether  the  monkeys  are  infected  via  the  brain  or 
the  brain  and  peritoneum  at  the  same  time.  According  to  other 
authors  it  does  not  matter  whether  the  injection  is  made  into  the 
subcutaneous  tissue,  the  nerves,  or  the  eyeball;  the  picture  is 
always  essentially  one  of  spinal  paralysis.  Usually  the  paralysis 
is  of  the  ascending  type  and  causes  death  by  involvement  of  the 
medulla  with  consequent  respiratory  paralysis.  Occasionally  bulbar 
signs  (facial  palsy,  &c.)  are  observed;  the  combination  of  bulbar 
and  spinal  symptoms  produces  a  clinical  picture  similar  to  that  of 
Landry's  disease  in  man.  Finally,  there  can  be  no  doubt  that 
monkeys  are  subject  to  a  purely  cerebral  form  of  the  disease, 
analogous  to  the  rare  human  cases  of  cerebral  Heine-Medin 
disease.  Marasmic,  abortive  and  relapsing  forms  of  the  disease 
have  been  observed.  In  short,  clinical  investigation  of  cases  of 
experimental  poliomyelitis  in  monkeys  reveals  types  similar  to  the 
manifold  forms  of  Heine-Medin  disease  in  man,  and  the  point  of 
entry  of  the  virus  does  not  influence  the  result. 

Prognosis. — One  important  point  of  difference  between  human 
poliomyelitis  and  the  experimental  disease  in  monkeys  is  the 
mortality.  The  figure  varies  in  human  beings,  as  has  been  shown 
above.  It  lies  between  10  and  20  per  cent.,  when  only  those  cases 
are  counted  in  which  paralysis  has  occurred.  Similar  statistics  in 
monkeys  show  a  much  less  favourable  figure.  In  my  own 
monkeys,  counting  only  those  in  which  paralysis  appeared,  I  find 
that  /6'4  per  cent,  died  of  the  paralysis,  6  per  cent,  survived 
paralysed  and  i/'6  per  cent,  recovered  completely-  These  figures 
are  very  similar  to  those  obtained  by  Flexner  and  Lewis.  They 
found  that  75  per  cent,  of  all  cases  with  paralysis  died.  This 
figure,  however,  is  only  an  estimate,  because  they  killed  many  of 
their  animals  for  purposes  of  investigation.  I  myself  waited  in 
almost  every  case  until  the  animal  was  moribund  before  killing  it. 
My  figures  are  consequently  quite  reliable.  Flexner  and  Lewis 
state  that  by  passing  a  virus  through  many  animals  they  obtained 
finally  a  mortality  of  100  per  cent.  The  prognosis  in  experimental 
poliomyelitis  of  monkeys  is  therefore  much  less  favourable  than 
that  of  natural  poliomyelitis  in  man.  This  is  of  importance  in 
judging  of  the  value  of  any  therapeutic  measures  when  applied  to 
the  experimental  disease. 

Fig.  16  shows  clearly  the  relations  between  duration  of  in- 
cubation and  duration  (i.e.,  severity)  of  paralysis;  it  illustrates  the 
question  of  recovery  and  duration   of  paralysis. 


ETIOLOGY   OF  THE   DISEASE 


61 


According  to  this  table  a  short  incubation  period  corresponds 
to  a  short  violent  course  of  the  disease.  In  the  case  of  monkey 
No.  2>7 >  however,  a  short  incubation  period  did  not  mean  a  sub- 
sequently fatal  attack.  Further  consideration  of  the  table  shows 
that  there  is  no  fixed  correspondence  between  the  length  of  the 
incubation  period  and  the  severity  of  the  attack.  Monkeys  Nos. 
13,  11,  and  35,  with  incubation  periods  of  10J,  n\,  and  15  days 
respectively,  suffered  from  a  long  paralytic  stage,  which  ended 
fatally;  but.  on  the  other  hand,  the  monkeys  Nos.  2  and  36  had 
an  equally  long  incubation  period  and  yet  died  very  rapidly.  We 
find  also  that  in  some  cases  (monkeys  Nos.  32  and  40),  in  spite 
of  a  relatively  short  incubation  period,  the  disease  ended  in  com- 
plete recovery. 


MonkeyN1. 
Days 


Period  of  incubation. 

,,  paralysis  ending  in  death. 

,,  non-fatal  paralysis. 

Fig.  16. 


The  conclusion  to  be  drawn  from  these  experiments  is  that 
no  rules  for  prognosis  can  be  formulated  which  are  based  upon 
the  length  of  the  period  of  incubation. 


III.— THE  NATURE  OF  THE  VIRUS. 

The  results  of  my  first  experiments  convinced  me  that  the 
virus  of  poliomyelitis  must  be  fairly  stable.  I  was  successful  in 
the  case  of  monkey  No.  1  in  inoculating  a  virus  which  had  been 
kept  for  forty-eight  hours  after  the  autopsy,  and  with  monkey 
No.   2  in  inoculating  one  kept  for  sixty-four  hours.     Flexner  and 


62 


EPIDEMIC   INFANTILE   PARALYSIS 


Lewis  came  to  the  same  conclusion;  they  used  a  virus  which  was 
thirty-eight  hours  old.  Landsteiner  and  Levaditi  used  a  virus  four 
days  after  the  death  of  the  child  in  their  original  experiment.  In 
his  fundamental  work  Landsteiner,  together  with  Popper,  made 
the  suggestion  that  the  cause  of  Heine-Aledin  disease  belonged  to 
the  group  of  viruses  capable  of  filtration.  The  following  experi- 
ments prove  the  correctness   of  his   suggestion. 

Filtration  Of  the  Virus. — Flexner  and  Lewis  demonstrated 
simultaneously  with  and  independently  of  Landsteiner  and  Levaditi 
that  the  virus  would  pass  through  various  filters  which  were  fine 
enough  to  hold  back  bacteria.  I  give  below  the  tabulated  results 
of  Landsteiner  and  Levaditi's  experiments;  from  them  can  be  seen 
the  difference  in  virulence  between  the  filtered  and  unfiltered  virus. 


Name  of  filter 


(Berkefeld      ... 

(Control 

fBerkefeld       ... 
b  \  Chamberland 
I  Control 

fBerkefeld     I 
c\  „  II 

(Control 

(Reichel  A     ... 
d\        ,,        B     ... 
(Control 


Monkey 


Macacus  cvnomoleits  N> 


Callitrichus  No.  26 
„     27 


iS 

19 
100 


Macacus  sinicus  No. 

!  )  •  !  5  ) 

, ,  rhesus    , , 


28 
31 


Macacus  rhesus  No.  23 
Macacus  cynomolgus  No.  24 
Mandrill  No.  2; 


Incubation 
period 


8  d 


ays 


16 
8 


11 
8 
4 


+  in  5  days 
Survived 
+  in  2  days 

Survived 
+  in  1  day 
+  in  2  days 

+  in  15  days 
+  in    2     ,, 

+  in    7     ,, 

+  in  5  days 

Killed 

+  in  1  day 


Landsteiner  and  Levaditi  and  also  Flexner  and  Lewis  proved 
that  a  living"  virus  was  present  in  the  filtrate  and  not  merely  a  toxin 
contained  in  the  spinal  cord,  by  injecting  the  spinal  cord  substance 
of  monkeys  infected  with  the  filtrate  into  other  monkeys  with  a 
positive  result. 

Leiner  and  v.  Wiesner  at  first  obtained  negative  results  when 
using  Reichel  filters;  later  they  obtained  positLe  results  with  virus 
passed  through  Pukall  filters.  Their  results  show  the  influence  of 
filtration  upon  the  length  of  the  incubation  period. 


Inoculation  with  filtrate 

Inoculation  with  unfiltered  emulsion 

Monkey  No. 

Incubation  period 

Monkey  No. 

Incubation  period 

22 
23 
36 
41 

10  days 

15      ,. 
12       ,, 

11  ,, 

21 
21 

37 
40 

8  days 
8     „ 
7     ,. 
6     ,, 

ETIOLOGY   OF  THE   DISEASE  63 

The  period  of  incubation  is  longer  when  the  filtered  virus  is 
used,  as  can  be  seen  from  both  tables.  Flexner  and  Lewis  state 
further  that  when  they  used  virus  which  had  been  intensified  by 
being"  passed  through  many  animals,  a  very  small  dose  of  the 
filtrate  produced  severe  paralysis  after  an  incubation  period  of  the 
usual  length;  they  conclude  that  the  virus  must  be  extraordinarily 
fine. 

Personally,  I  had  but  little  success  with  emulsions  filtered 
through  a  Berkefeld  filter;  I  was  able  only  indirectly  to  prove 
that  the  filtrate  contained  the  virus  by  showing"  that  a  monkey 
which  had  been  inoculated  with  it  without  result  was  immune  to  a 
lethal  dose  of  the  emulsion. 

These  experiments  prove  that  the  virus  is  capable  of  passing 
through  filters  like  the  Berkefeld,  Chamberland,  Reichel,  and 
Pukall  filters,   through  all   of  which  bacteria  cannot  pass. 

Resistance  to  Glycerine. — In  its  behaviour  towards  filters  the 
poliomyelitis  virus  shows  again  its  similarity  to  the  virus  of  rabies; 
on  the  whole  it  seems  to  pass  through  filters  more  easily  than  the 
latter  virus.  This  led  to  further  experiments  being  made  to 
discover  further  similarities.  One  of  the  most  important  of  these 
is  the  resistance  shown  towards  glycerine.  Landsteiner  and 
Levaditi  made  the  first  experiment ; '  in  their  first  experiment  they 
used  with  success  a  virus  which  had  been  preserved  in  33  per  cent. 
glycerine  for  four  days,  in  order  that  it  might  be  sent  from  Vienna 
to  Paris.  We  ourselves,  usually  against  our  inclination  and  only 
because  our  modest  means  did  not  always  allow  us  to  inoculate 
direct  from  one  monkey  to  another,  had  ample  opportunity  of 
studying  the  resistance  to  glycerine  of  our  virus.  In  the  following 
table  I  have  put  together  all  the  injections  in  which  virus  preserved 
with  glycerine  was  used;  each  original  virus  is  placed  in  a  separate 
table. 

It  is  clear  that  the  virus  remains  potent  for  at  least  ninety-one 
days  when  kept  in  50  per  cent,  glycerine,  but  this  does  not  represent 
the  limit  of  time  that  it  can  be  kept  (cf.  monkeys  Nos.  46,  59,  and 
61).  Although  the  inoculation  of  monkey  No.  44  with  virus  which 
had  been  kept  for  95  days  resulted  only  in  a  doubtful  illness,  the 
reason  of  this  is  to  be  found  rather  in  a  peculiar  resistance  of  this 
particular  animal  than  in  the  virus  itself.  The  experiments  with 
virus  No.  6  shows  that  142  days  in  pure  glycerine  is  not  enough 
to  cause  any  diminution  of  potency.  There  is  some  slight  differ- 
ence in  behaviour  towards  glycerine  between  the  virus  obtained  direct 
from  man  and  that  obtained  from  inoculated  animals.  Yet  experi- 
ments with  virus  Nos.  11  and  12  show  that  after  passing  through 
five  and  six  animals  the  virus  resists  glycerine  as  well  as  the 
original  virus  (cf.  monkeys  Nos.  59  and  61). 

These  results  correspond  with  those  obtained  by  Landsteiner 
and  Levaditi;  these  authors  supplement  my  figures  in  so  far  as 
they  used  33  per  cent,  glycerine  in  their  experiments.  They  proved 
that  the  virulence  was  not  affected  after  seven,   nine,   and  twenty- 


64 


EPIDEMIC   INFANTILE   PARALYSIS 


two  days  in  33  per  cent,  glycerine.     Flexner  and  Lewis  also  have 
proved  the  resistance  of  the  virus  to  glycerine. 

The  discovery  of  this  fact  is  of  great  practical  importance; 
experimental  work  is  rendered  easier  by  the  knowledge  that  direct 
inoculation   from  monkey  to  monkey  is  not  necessary.     Glycerine 


Virus  No.   11. 

Preserved  in  50%  Glycerine. 


No.  of  monkeys 

No.  of 

Method  of 

Length  of  time 

Length  of 

Duration  of  the 

passed  through 

monkey 

infection 

in  glycerine 

incubation  period 

fatal  illness 

Original  virus 

44 

i-c.  and  i-p. 

95  days 

12  days 

Abortive  p.m.  ? 

III 

23 

,, 

14     ,, 

5i      ,. 

3  days 

III 

46 

9i     „ 

8      ,, 

5     » 

V 

47 

)» 

24     ,, 

9      „ 

Survived 

V 

48 

,, 

24     ,, 

9      ,, 

2  days 

V 

58 

l-C. 

78     „ 

10      ,, 

2     ,, 

V 

59 

9i       „ 

10      ,, 

Survived 

V 

61 

,, 

91     >. 

4      ,, 

ih  days 

VI 

56 

i-c.  and  i-p. 

30     ,, 

13      „ 

9       » 

Virus  No.    12. 

Preserved  in  50%  Glycerine. 


Xo.  of  monkeys 

No.  of 

Method  of 

Length  of  time 

Length  of 

Duration  of  fatal 

passed  through 

monkey 

infection 

in  glycerine 

incubation  period 

illness 

Original  virus 

21 

l-c.  and  i-p. 

31 

days 

9  days 

i\  days 

11 

29 

l-C. 

8 

,, 

8     ,, 

7       ,. 

II 

27 

,, 

3i 

, 

8     ,, 

4        >> 

II 

37 

,, 

3i 

6     ,, 

Survived 

II 

38 

,, 

3i 

, 

8     „ 

2it  days 

II 

40 

i-c.  and  i-p. 

33 

, 

7     „ 

Survived 

III 

43 

,, 

8 

, 

9     ,, 

Abortive  p.m. 

III 

42 

l-C. 

10 

, 

10     ,, 

i\  days 

III 

35 

-c.  and  i-p. 

20 

, 

15     » 

I?                 !! 

A" 

49 

l-C. 

24 

' 

12     ,, 

Survived 

Virus  No.  6. 

Preserved  in  Concentrated  Glycerine. 


Xo.  of  monkeys         Xo  of  Method  of  Length  of  time 

passed  through     j    monkey  infection  in  glycerine 


Length  of  Duration  of  fatal 

incubation  period  j  illness 


i-c.  and  i-p.     59  days 
142   ,, 


10  days 
54  „ 


5  days 
I  day- 


Can  be  used  as  a  preservative  when  the  virus  has  to  be  sent  from 
place  to  place.  Especially  is  it  important  in  cases  of  suspected 
Heine-Medin  disease,  when  the  virus  may  be  kept  in  50  per  cent. 
glycerine  until  a  monkey  can  be  procured.  Preservation  in  glycerine 
may  be  used  for  material  that  has  become  contaminated  with 
bacteria;  in  50  per  cent,  glycerine  the  bacteria  are  slowly  destroyed. 


ETIOLOGY  OF  THE  DISEASE  05 

The  Effect  of  Low  and  High  Temperatures— The  behaviour 
of  the  virus  towards  different  temperatures  presents  various  points 
of  interest.  The  above  figures  relating  to  the  resistance  to 
glycerine  provide  some  data  owing  to  the  fact  that  all  the  pre- 
parations were  kept  in  the  dark  in  an  ice-chest.  It  follows  that  a 
temperature  of  +  40  C.  is  not  inimical  to  a  virus  preserved  in 
glycerine.  Flexner  and  Lewis  found  that  keeping  the  virus  itself 
at  the  temperature  of  an  ice-chest  for  fifty  days  had  no  effect  upon 
its  virulence;  even  complete  mouldiness  of  the  pieces  of  spinal 
cord  containing  virus  did  not  influence  the  activity  of  the  virus. 
They  kept  virus  at  a  temperature  of  between  —  2°  and  —  40  f or 
forty  days  and  still  found  it  virulent.  Leiner  and  v.  Wiesner  used 
a  virus  which  had  been  kept  for  four  hours  in  a  freezing  mixture; 
an  intracerebral  injection  produced  slight  paralysis  after  an  incuba- 
tion period  of  twelve  days.  Landsteiner  and  Levaditi  quote  one 
case  in  which  the  virus  was  kept  for  eleven  days  in  the  frozen 
state  and  then  caused  paralysis  of  the  hind  limbs  after  an  incubation 
period  of  six  days;  the  animal  survived. 

These  experiments  prove  that  the  virus  of  Heine-Medin  disease 
is  but  little  affected  by  low  temperatures.  As  will  be  seen  later,, 
this  has  some  bearing  on  the  question  of  epidemiology. 

There  is  some  accidental  evidence  showing  the  behaviour  of 
the  virus  towards  moderate  temperatures.  Landsteiner  and 
Levaditi,  in  the  course  of  their  attempts  to  obtain  an  attenuated 
virus  by  methods  similar  to  that  employed  by  Pasteur  in  the  case 
of  rabies,  found  the  virus  fully  virulent  after  nine  days,  at  a 
temperature  of  220  C.  In  his  experimental  "  cultures,"  quoted  on 
pag'e  29,  Levaditi  showed  that  the  virus  resisted  a  temperature  of 
370  for  at  least  fifteen  days. 

The  virus  appears  to  be  much  affected  by  temperatures  higher 
than  these.  We  have  made  systematic  experiments  to  elucidate 
this  point. 

Experiment  1. — Monkey  No.  32  received  an  intracerebral  injection  on 
February  7,  1910,  of  '5  c.c.  of  a  5  per  cent,  emulsion  of  brain  and  spinal 
cord  heated  for  half  an  hour  to  a  temperature  of  450.  The  material  was 
obtained  from  monkey  24  (virus  No.  12  passed  through  two  animals).  On 
February  15  paresis  of  the  hind  limbs,  increasing  for  a  few  days,  dimin- 
ishing from  February  22  onwards  until  March  12.  No  paralysis  is  present. 
The  control,  monkey  29,  received  '35  c.c.  of  the  same  virus  unheated, 
became  paralysed  on  the  13th  and  died  on  the  15th  (vide  p.  47). 


Experiment  2. — Monkey  51,  on  April  25,  1910,  received  an  intracerebral 
injection  of  '5  c.c.  of  5  per  cent,  emulsion  from  monkey  36  (virus  No.  11 
passed  through  five  animals].  The  emulsion  was  heated  for  half  an  hour  at 
temperature  of  500.  The  animal  remained  well.  The  same  virus,  injected  un- 
heated  on  May  31,  1910,  into  monkey  58,  proved  highly  virulent  (vide  p.  77). 


Experiment   3. — Monkey  26,    on   January   25,    1910,    received   '5    c.c.    of 
10  per  cent,  emulsion  of  brain  and  cord  of  monkey  21    (virus  No.   12  passed 


66  EPIDEMIC   INFANTILE  PARALYSIS 

through  one  animal).  The  emulsion  was  heated  for  half  an  hour  at  550.  The 
animal  remained  well.  Monkey  24  injected  on  the  same  day  with  the  same 
amount  of  virus  unheated  became  paralysed  in  both  legs  on  the  fourth  day 
and  died  on  the  fifth.      Microscopical  appearances  typical. 

When  heated  for  half  an  hour  at  450  the  virus  is  still  virulent, 
although  somewhat  attenuated;  heating  for  half  an  hour  at  500 
or  550  was  sufficient  to  destroy  its  virulence. 

Leiner  and  v.  Wiesner  obtained  similar  results.  They  found 
the  virus  no  longer  virulent  after  being  heated  to  500  for  one 
hour  and  to  6o°  for  fifteen  to  twenty  minutes.  It  was  due  probably 
to  some  peculiarity  in  the  animal  used  that  they  found  in  one 
instance  that  heating  for  two  hours  at  a  temperature  of  350 
destroyed  the  activity  of  the  virus;  Levaditi's  experiment,  quoted 
above,  with  virus  at  370,  and  my  own  experience  with  virus  kept 
at  450,  confirm  this  view.  Flexner  and  Lewis  report  that  warming 
at  450  to  500  for  half  an  hour  destroys  the  potency  of  the  virus; 
this  corresponds  more  or  less  with  our  own  results. 

Resistance  to  Drying. — The  evidence  on  this  point  is  some- 
what   conflicting.     The    following    is    my    own    experiment :  — 

Monkey  36  {Macacus  rhesus)  was  injected  with  virus  No.  11  on 
February  26,  iqio.  The  virus  was  obtained  from  the  cord  of  a  monkey 
which  had  been  dried  in  vacuo  for  twenty-eight  days  at  room  temperature 
and  guarded  from  light.  After  an  incubation  period  of  thirteen  days 
paralysis  of  the  right  fore  limb  and  of  both  limbs  appeared;  on 
March  13,  total  paralysis  of  the  hind  limbs;  on  March  14,  paralysis  of  all 
limbs;  death  on  March  15.     Histological  appearances  typical. 

Spinal  cord  dried  for  twenty-eight  days  in  vacuo  was  found 
therefore  to  be  virulent.  The  experience  of  other  authors  has 
been  similar.  Flexner  and  Lewis  dried  the  virus  for  seven  days 
over  caustic  potash  and  found  it  virulent;  Landsteiner  and  Levaditi, 
following  Pasteur's  method,  dried  a  cord  over  caustic  potash  in 
one  case  for  nine  days,  in  another  for  twenty-four  days,  at  a  tem- 
perature of  220.  In  both  experiments  the  cord  was  found  to  be 
virulent.  They  emphasise  the  difference  in  this  respect  of  the  virus 
of  Heine-Medin  disease  and  the  virus  of  rabies.  In  another  experi- 
ment they  dried  a  thick  layer  of  emulsion  of  virulent  spinal  cord 
in  vacuo  at  room  temperature  and  found  it  fully  virulent  at  the 
end  of  fifteen  days. 

On  the  other  hand,  Leiner  and  v.  Wiesner  obtained  a  different 
result.  They  dried  a  thin  layer  of  emulsion  in  an  incubator  at 
.37°  for  four  hours  and  found  it  non-virulent.  In  another  instance 
they  allowed  a  thin  layer  of  emulsion  of  spinal  cord  to  dry  for  twenty- 
four  hours  at  the  temperature  of  the  room;  the  dried  emulsion  was 
washed  off  and  injected  with  a  negative  result  (unfortunately,  they 
do  not  give  any  report  of  a  control  experiment).  In  this  experi- 
ment they  were  attempting  to  reproduce  the  natural  conditions  and 
it   is   possible   that   in   a   very   thin   layer   the    emulsion    withstands 


ETIOLOGY   OF  THE   DISEASE  67 

drying  less  well.     From  this  point  of  view  it  would  be  worth  while 
to   corroborate   and  amplify  their  results. 

Behaviour  towards  Disinfectants. — I  have  not  been  in  a  posi- 
tion to  make  extended  experiments  on  the  behaviour  of  the  virus 
of  poliomyelitis  towards  disinfectant  chemicals,  although  the 
subject  is  of  the  greatest  importance  for  many  reasons,  particularly 
from  the  point  of  view  of  prophylaxis.  I  made  experiments  with 
formalin.  The  chemical  was  not  mixed  directly  with  the  virus, 
but  an  active  emulsion  was  exposed  to  the  vapour  in  the  course 
of  a  test  disinfection  of  a  room  which  will  be  described  later.  The 
virulence  of  the  emulsion  was  found  to  have  been  destroyed.  The 
most  complete  investigations  into  the  effect  of  chemicals  upon  the 
virus  have  been  made  by  Landsteiner  and  Levaditi.  Their  first 
experiments  were  made  with  menthol  oil  and  with  a  powder  com- 
posed of  menthol,  salol,  and  boric  acid.  Two  cubic  centimetres  of 
an  emulsion  of  virulent  virus  was  shaken  with  "5  c.c.  of  a  1  per 
cent.  solution  of  menthol  oil  and  allowed  to  stand  for  two  hours 
at  room  temperature.  A  monkey  which  received  an  intracerebral 
injection  of  "5  c.c.  of  this  mixture  showed  only  slight  transient 
symptoms;  the  control  animal  became  paralysed  on  the  fourth  day 
and  died  on  the  sixth.  In  a  second  experiment  2  c.c.  of  the  same 
emulsion  was  mixed  with  "05  grm.  of  the  powder  ("2  grm.  menthol, 
5  grm.  salol,  20  grm.  boric  acid),  well  shaken  and  kept  at  room 
temperature  for  two  hours.  The  monkey  injected  with  this  also 
suffered  from  transient  symptoms. 

A  1  in  1,000  watery  solution  of  thymol  mixed  with  an  equal 
quantity  of  emulsion  for  one  hour  at  370  did  not  diminish  the 
virulence.  The  activity  of  the  virus  was  destroyed  after  mixture 
with  a  2  per  1,000  solution  of  potassium  permanganate  for  one 
hour  at  370.  A  1  in  5  (6  per  cent.)  dilution  of  perhydrol  (Merck) 
mixed  with  an  equal  part  of  emulsion  for  forty-five  minutes  at 
370  killed  the  virus.  Flexner  and  Lewis  found  a  1  per  cent,  solu- 
tion of  H202  was  effective,  but  do  not  give  the  length  of  contact 
necessary. 

Of  some  importance  with  regard  to  personal  prophylaxis  is 
the  discovery  by  Landsteiner  and  Levaditi  of  the  efficacy  of 
potassium  permanganate  and  peroxide  of  hydrogen. 

Kraus  investigated  the  influence  of  carbolic  acid  on  the  virus. 
He  found  that  the  filtered  emulsion  is  more  easily  killed  than  the 
unfiltered;  this  is  due  to  the  presence  in  the  latter  of  coarser 
particles  of  the  spinal  cord,  which  enclose  the  virus  and  prevent 
the  carbolic  from  acting  on  it.  Contact  with  a  '5  per  cent,  solution 
of  carbolic  acid  for  five  days  lessened  the  virulence  and  in  some 
cases  destroyed  it.  A  i  per  cent,  solution  did  not  kill  the  virus 
in  one  to  three  days,  but  it  was  efficacious  in  four  to  five  days. 

The  Durability  of  the  Virus  in  Animals. — My  own  material 
bearing  on  this  point  is  small.  In  general  I  used  only  the  emul- 
sions obtained  from  the  brain  and  cord  of  animals  which  had 
died  acutely   for  further  injections.     The   spinal   cord   of   monkeys 


68  EPIDEMIC   INFANTILE   PARALYSIS 

which  had  died  on  the  fourth  day  after  infection  proved  fully 
virulent.  That  the  virus  can  remain  virulent  for  a  long  time  within 
the  body  of  the  animal  is  proved  by  the  case  reported  above  {vide 
p.  59);  monkey  11  received  an  intracerebral  injection  on  Decem- 
ber 8,  1909;  paralysis  set  in  on  the  26th  and  then  improved 
for  a  time ;  on  January  9  a  definite  relapse  occurred  and  the  animal 
died  on  January  11.  The  typical  appearances  of  acute  poliomyelitis 
found  in  the  spinal  cord,  together  with  the  results  of  further 
injections  into  other  animals,  proved  that  the  virus  was  still  fully 
virulent  after  thirty-three  days.  Leiner  and  v.  Wiesner  found  potent 
virus  in  the  cord  of  an  animal  which  had  been  ill  for  twenty-four 
days.  It  is  probable,  however,  that  these  results  do  not  represent 
the  normal  condition  of  affairs;  relapses  are  very  rare  in  monkeys 
and  I  have  only  seen  one  case.  In  another  case  Leiner  and  v. 
Wiesner  found  that  the  spinal  cord  of  a  monkey,  which  had 
suffered  from  paralysis  for  only  six  days,  was  no  longer  virulent; 
the  monkey  which  was  injected  with  this  cord  showed  no  signs 
of  paralysis  up  to  the  twenty-fourth  day.  Landsteiner  and  Levaditi 
found  virulent  spinal  cord  on  the  fourth  day  after  injection,  but 
thirty-nine  to  forty-five  days  later  they  found  no  virulence. 

Xo  rule  as  to  the  viability  of  the  virus  in  monkeys  can  be 
formulated  from  the  small  amount  of  material  available.  There  is 
a  wide  field  for  further  investigation  in  this  direction.  Landsteiner 
and  Levaditi  suppose  that  the  virus  usually  disappears  at  the  end 
of  the  acute  stage,  but  that  in  isolated  instances  this  does  not 
take  place. 

The  virus  appears  to  remain  longer  in  regions  other  than  the 
central  nervous  system.  Flexner  reports  that  Osgood  and  Lukas, 
two  American  investigators,  found  the  mucous  membrane  of  the 
pharynx  virulent  six  months  after  the  monkey  had  received  an 
intracerebral  injection,  and  at  a  time  when  the  virus  had  completely 
disappeared  from  the  central  nervous  system.  In  another  case  the 
brain,  spinal  cord,  and  mucous  membrane  of  the  nose  and  throat 
were  all  virulent  eight  weeks  after  the  intracerebral   injection. 

The  Effect  of  passing  the  Virus  through  Animals. — The 
question  whether  the  biological  characteristics  of  the  virus  become 
altered  when  it  is  passed  through  animals  is  of  great  interest. 
The  material  available  is  not  large.  According  to  my  own  experi- 
ence the  behaviour  towards  glycerine  is  the  same  in  the  original 
virus  and  in  virus  which  has  been  passed  through  animals;  I  have 
found  no  constant  difference  in  virulence  (pathogenic  energy) 
towards  monkeys  between  them.  Leiner  and  v.  Wiesner  found  no 
diminution  of  virulence  after  a  "  long  "  series  of  reinoculations. 
Flexner  and  Lewis,  who  have  passed  virus  through  longer  series 
of  animals  than  anyone  else,  have  come  to  the  conclusion  that  the 
virus  becomes  more  powerful,  or,  at  any  rate,  loses  none  of  its 
potency  and  becomes  more  constant  in  its  effect.  This  increase  in 
constancy  is  shown  in  three  ways:  (1)  The  higher  proportion  of 
fatal   cases;   (2)   the   higher   percentage   of   successful   intracerebral 


ETIOLOGY  OF  THE  DISEASE  69 

inoculations  (100  per  cent,  instead  of  75  per  cent,  with  the  original 
virus) ;  and  (3)  a  greater  uniformity  in  the  duration  of  the  incubation 
period.  These  experiences  remind  one  of  the  results  obtained  by 
Pasteur  in  hydrophobia;  he  found  that  the  virulence  towards  rabbits 
was  increased  by  passing  the  virus  through  a  large  number  of 
rabbits;  intracerebral  inoculation  acted  more  certainly  and  with  a 
shorter  incubation  period.  We  know  now,  however,  that  the  term 
exaltation  of  the  virus  must  be  used  cum  grano,  because  the 
"  exalted  "  virus  is  less  potent  than  the  ordinary  kind,  when 
administered  subcutaneously.  At  any  rate,  some  peculiar  biological 
change  does  take  place  in  the  virus,  and  we  are  inclined  to  regard 
it  as  the  essential  factor  underlying  protective  inoculation  against 
hydrophobia.  The  observations  of  Flexner  and  Lewis  make  it  not 
improbable  that  continued  passage  through  monkeys  causes  some 
biological  change  in  the  pm.  virus,  turning  it  into  a  kind  of 
"  virus  fixe,"  as  shown  by  the  greater  constancy  of  the  incubation 
period,  of  the  morbidity  and  of  the  mortality.  Further  investiga- 
tions must  be  made  to  find  out  if  the  changes  produced  in  this 
manner  can  be  demonstrated  by  other  means. 

Flexner  and  Lewis  have  called  attention  to  a  point  which  is 
of  importance  in  this  connection.  They  assume  that  the  sudden 
change  from  man  to  monkey  ("  change  of  host  ")  must  have  a  con- 
siderable effect  upon  the  virus  because  it  is  so  often  destroyed  in  the 
process.  My  own  experience  confirms  this  in  some  measure;  cf 
the  five  original  examples  of  virus  I  succeeded  in  transmitting  only 
three  to  monkeys.  We  must  regard  it  as  a  possibilhy  that  the 
transference  of  the  virus  to  monkeys  causes  some  biological  change 
in  the  virus.  The  present  state  of  our  knowledge  does  not  admit 
of  any  more  definite  statement.  A  wide  field  is  left  open  in  this 
direction  also  to  future  experimenters. 

IV.— THE  USE  OF  OTHER  ANIMALS  FOR 
EXPERIMENT. 

The  Susceptibility  of  Different  Animals. — It  would  be  a  great 
advantage  if  some  other  animal,  more  easy  to  obtain  and  keep  and 
less  costly,  could  be  submitted  for  the  monkey.  I  have  experi- 
mented with  white  mice,  guinea-pigs,  sheep,  goats,  and  dogs;  using 
the  method  of  intracerebral  injection,  which  proved  the  best  in  the 
case  of  monkeys,  I  nevertheless  was  unable  to  produce  any  sym- 
ptoms of  poliomyelitis  in  these  animals.  In  all  the  experiments  the 
brain  and  spinal  cord  emulsions  proved  entirely  non-virulent, 
although  the  same  emulsion  injected  into  monkeys  produced 
typical  lesions  of  poliomyelitis.  Other  observers  (Leiner  and  v. 
Wiesner,  Landsteiner  and  Levaditi,  Krause  and  Meinicke,  Flexner 
and  Lewis)  obtained  the  same  negative  results.  Flexner  and  Lewis 
even  used  pigs,  horses,  cows,  and  cats;  they  observed  the  animals 
for   weeks   after   the   injection   but   they   never   saw   any   paralysis. 


JO  EPIDEMIC   INFANTILE  PARALYSIS 

Leiner  and  v.  Wiesner,  and  also  Landsteiner  and  Levaditi,  used 
young  dog's  and  injected  the  virus  both  into  the  brain  and  the 
peritoneum,  but  they  obtained  no  single  positive  reaction.  The 
same  authors  and  Krause  and  Meinicke  have  proved  that  fowls 
and  pigeons  are  not  susceptible.  It  is  quite  certain  therefore  that 
all  the  animals  mentioned  are  not  susceptible  to  the  virus  of 
poliomyelitis.  This  negative  finding  is  of  importance  in  judging 
the  assumption  which  is  made  frequently,  that  the  occurrence  of 
paralysis  in  animals,  particularly  fowls  and  dogs,  can  be  connected 
with  epidemics  of  Heine-Medin  disease. 

Earlier  Experiments  with  Rabbits. — There  has  been  much 
controversy  about  the  susceptibility  of  rabbits.  The  rabbit  was 
the  first  animal  used  for  experimental  injection  of  material 
obtained  from  children  who  had  died  of  paralysis.  The  first 
attempt  was  made  in  1899  by  Biilow-Hansen  and  Harbitz.  They 
injected  emulsion  of  the  spinal  cord  and  cerebro-spinal  fluid  into 
rabbits  and  mice,  using  the  intracerebral  method  among  others. 
The  results  were  all  negative.  The  experiments  of  Guinon  and 
Rist  (1903),  in  which  cerebrospinal  fluid  from  cases  of  poliomyelitis 
was  injected  into  rabbits,  led  to  no  positive  results.  In  1908, 
Pasteur,  Foulerton,  and  MacCormac  reported  positive  results  with 
rabbits  for  the  first  time.  They  injected  cerebrospinal  fluid, 
obtained  eleven  days  and  four  weeks  after  the  commencement  of 
the  disease,  into  rabbits;  in  some  the  injection  was  subcutaneous, 
in  others  intraperitoneal,  and  finally  intracerebral.  Many  of  these 
animals  became  paralysed  some  time  after  the  injection;  the 
authors  report  that  in  a  few  cases  they  were  able  to  infect  other 
rabbits  with  the  cerebrospinal  fluid  of  these  first  rabbits,  but  that 
it  was  not  possible  to  transmit  the  disease  to  a  third  generation. 
Histological  examination  of  the  spinal  cord  of  one  of  the  paralysed 
rabbits  showed   ho   changes   characteristic  of  poliomyelitis. 

Krause  and  Wernicke's  Experiments  with  Rabbits. — The 
experiments  of  the  English  authors  raised  hopes  that  poliomyelitis 
might  be  produced  experimentally  in  rabbits  and  their  experiments 
were  repeated  by  Krause  and  Meinicke  in  the  summer  of  1909  at 
the  time  of  the  great  Westphalian  epidemic.  These  authors  used 
"large  doses"  of  cerebrospinal  fluid  obtained  from  autopsies  or 
by  lumbar  puncture;  the  injections  were  intraperitoneal,  intravenous 
or  subdural.  Very  many  of  the  animals  became  ill  after  the  in- 
jection, and  Krause  and  Meinicke  observed  "  a  certain  regularity  in 
the  period  of  time  elapsing  before  the  illness  began,  in  the 
character  of  the  symptoms  and  in  the  total  duration  of  the  illness. 
Death  was  ushered  in  by  symptoms  which  pointed  to  a  lesion  of 
the  spinal  cord."  In  their  first  paper  Krause  and  Meinicke  do  not 
record  any  microscopical  examinations.  They  found  that  spleen 
pulp,  blood,  and  cerebrospinal  fluid  of  rabbits  dying  of  polio- 
myelitis were  suitable  for  further  transmission  of  the  disease  as 
well  as  the  brain  and  spinal  cord.  It  is  to  be  noted  that  the  disease 
consisted  of  the  above  peculiar  symptoms. 


ETIOLOGY  OF  THE  DISEASE  7 1 

Results  Of  Personal  Experiments. — In  my  first  experiments 
I  used  rabbits  bred  in  the  laboratory.  The  animals  were  full  grown 
and  weighed  from  2,000  to  3,000  grin.  I  chose  adult  rabbits  which 
were  already  acclimatized  to  the  laboratory,  because  young  rabbits 
are  known  to  succumb  readily  to  secondary  infections.  The  first 
experiments  with  their  results  are  as  follows :  — 

Experiment  1. — Cerebrospinal  fluid  was  obtained  by  lumbar  puncture 
from  a  3-year-old  child  who  had  suffered  from  paralysis  for  three  weeks 
and  was  in  the  chronic  stage  of  the  disease.  The  fluid  was  kept  in  an 
incubator  at  temperature  37°  for  ten  days  in  order  to  "  exalt  "  the  virus. 
An  intracerebral  injection  of  '2  c.c.  was  made  into  two  rabbits.  Both 
animals  remained  quite  well. 


Experiment  2. — Fluid  was  obtained  by  lumbar  puncture  from  a  very 
acute  and  extensive  case  which  died  twenty-four  hours  later  and  showed 
typical  microscopial  changes  in  the  cord.  The  virus  was  "  exalted  "  for 
seven  days,  as  in  Experiment  1,  and  '2  c.c.  was  injected  into  two  rabbits. 
Both  remained  well. 


Experiment  3. — '2  c.c.  of  the  fluid  from  the  case  used  in  Experiment  1, 
but  obtained  fourteen  days  later,  was  injected  into  two  rabbits.  The  one 
died  of  suppuration  from  a  bite  on  the  abdomen ;  on  microscopical  examina- 
tion the  brain  and  spinal  cord  were  normal.  The  other  animal  remained 
well.  Two  other  animals  received  an  intracerebral  injection  of  '2  c.c.  of 
the  same  virus  passed  through  a  Berkefeld  filter;  they  remained  well. 
Finally  '2  c.c.  of  the  blood  of  this  case  was  injected  into  a  rabbit,  which 
remained  unaffected. 


Experiment  4. — Fluid  was  obtained  from  a  baby,  9  months  old,  suffering- 
from  paralysis  of  moderate  degree  for  seven  days.  Two  rabbits  each 
received  an  intracerebral  injection  of  '1  c.c.  and  both  remained  well. 

These  results  contradict  the  experience  of  Krause  and  Meinicke,  who 
found  cerebrospinal  fluid  suitable  for  the  transmission  of  the  disease.  It 
should  be  noted  further  that  in  some  of  my  experiments  the  fluid  was 
obtained  from  acute  and  severe  cases.  The  attempt  to.  "  exalt  "  the  virus 
in  the  incubator  cannot  have  affected  its  virulence.  The  entirely  negative 
character  of  the  results  made  me  sceptical  about  those  reported  by  Krause 
and  Meinicke.  On  the  other  hand,  this  fact  proved  nothing  against  the 
possibility  that  rabbits  might  be  susceptible  to  the  disease  and  so  of  use  in 
research.  On  the  one  hand,  it  was  doubtful  if  the  cerebrospinal  fluid  con- 
tained virus  at  all,  and,  on  the  other  hand,  whether  it  contained  a  sufficient 
quantity  of  the  virus. 

In  my  subsequent  experiments  I  always  used  material  which 
I  was  certain  contained  virus,  i.e.,  emulsion  of  the  brain  and 
spinal  cord  of  human  beings  and  monkeys  known  to  have  died 
of  the  disease. 

Experiment  5. — An  emulsion  of  virus  No.  6  was  injected  into  six 
rabbits,  two  by  intravenous  injection  ('5  c.c),  two  intraperitoneal  ('5  c.c), 
and  two    intracerebral    ('2    c.c).     All   remained    well,    although    a    monkey 


72  EPIDEMIC   INFANTILE   PARALYSIS 

injected    with   the    same   material    died   of  acute,    severe   poliomyelitis,    and 
material  from  this  monkey  proved  fully  virulent. 

In  consequence  of  these  results  1  felt  bound  to  advise  caution 
in  judging"  of  the  value  of  reports  of  positive  results  obtained  with 
rabbits.  The  rabbit  is  known  to  be  a  very  sensitive  animal  and 
this  has  several  times  led  to  much  confusion  in  etiological  in- 
vestigations; the  French  have  even  called  it  an  "  animal  capricieux." 

Subsequent  investigations  confirmed  my  previous  conclusions. 
Each  original  virus,  which  I  described  on  pp.  34-42,  was  injected 
into  rabbits  as  well  as  into  monkeys.  I  shall  not  describe 
the  results  obtained  with  virus  2  and  3,  because  no  definitely 
positive  result  was  obtained  with  these  in  monkeys.  Injection  of 
these  strains  into  rabbits  remained  without  any  effect.  The  follow- 
ing description  relates  only  to  those  strains  with  which  a  positive 
result  was  obtained  in  monkeys. 

Experiment  6. — Original  virus  No.  11  injected  into  six  rabbits,  three 
intraperitoneal  and  three  intracerebral.  A  5  per  cent,  emulsion,  which  had 
been  allowed  to  stand  for  a  time  in  order  to  separate  the  larger  particles, 
was  used;  the  dose  was  '2  c.c.  for  intracerebral,  and  3  c.c.  for  intraperitoneal 
injection.  All  the  rabbits  remained  well,  while  monkeys  (a),  (b)  and  No.  11 
died  with  typical  paralysis  [cf.  p.  41). 


Experiment  7. — A  20  per  cent,  emulsion  of  original  virus  No.  12  was 
used.  Six  rabbits  received  injections  :  two  intracerebral  ('2  c.c),  two  intra- 
peritoneal <3'5  c.c),  and  two  intravenous  (2  c.c.  of  emulsion  filtered  through 
paper).  One  rabbit  which  received  an  intracerebral  injection  died  of  pleuro- 
pneumonia on  the  twenty-third  day ;  one  of  the  intravenous  cases  died  on 
the  sixteenth  day  of  some  unknown  cause  ;  the  brain  and  spinal  cord  of  this 
animal  showed  no  pathological  changes  (another  rabbit  which  had  received 
no  injection  happened  to  die  on  the  same  day,  and  in  this  animal  also  we 
failed  to  find  any  cause  of  death).  The  rest  of  the  rabbits  remained  well. 
Monkeys  Nos.  4  and  13,  infected  with  this  emulsion,  died  with  typical 
poliomyelitis. 

Xo  injection,  therefore,  was  successful  in  which  virus  obtained 
direct  from  human  beings  was  used.  In  the  following  cases  virus 
was  used  which  had  been  passed  through  monkeys. 

Experiment  8. — With  an  emulsion  of  virus  No.  11,  passed  through  one 
monkey,  injections  were  made  into  eight  rabbits  on  December  17;  four 
intraperitoneal  (4  c.c),  four  intracerebral  ('2  c.c).  One  of  the  latter  died 
on  the  twenty-first  day  from  pleuropneumonia.  All  the  rest  remained  well. 
Monkeys  Nos.  14  and  5  became  ill  on  the  ninth  and  seventh  day,  and  died 
with  typical  paralysis  on  the  third  and  fourth  day  later.  Typical  -post- 
mortem changes  (cf.  pp.  48  and  155). 


Experiment  q. — On  December  24  six  rabbits  were  injected  with  an 
emulsion  of  virus  No.  11,  passed  through  two  monkeys;  three  injections 
were  intravenous  (2  c.c.  of  emulsion  filtered  through  paper),  and  three 
intracerebral  ('2  c.c).  All  remained  well.  Monkey  No.  15,  injected  on  the 
same  day,  became  ill  on  the  eighth  day,  and  died  of  paralysis  two  days  later. 
Typical  changes  -post-mortem. 


ETIOLOGY   OF  THE   DISEASE  73 

Experiment  10. — On  December  28,  1909,  five  rabbits  received  an  intra- 
cerebral injection  ('2  c.c.)  of  a  5  per  cent,  emulsion  of  virus  Xo.  11,  passed 
through  two  monkeys.  The  animals  remained  well.  Monkey  Xo.  16  was 
injected  with  the  same  emulsion;  it  became  paralysed  on  the  sixth  day,  and 
died  on  January  5,   1910.     Post-mortem  appearances  typical. 

It  is  necessary  for  me  to  discuss  these  results  more  fully  than  I  have 
done  so  far,  because  Krause  and  Meinicke  have  stated,  in  the  Deutsche 
med.  Wochensch?-.,  19 10,  14/15,  that  they  are  justified  in  not  considering 
my  experiments  to  be  unobjectionable  repetitions  of  their  own;  in  another 
place  these  authors  say  their  results  cannot  be  interpreted  otherwise  than 
in  their  own  sense  unless  "  unobjectionable  repetitions "  of  the  experiments 
lead  to  different  results.  In  my  opinion  no  objection  can  be  brought  against 
my  own  experiments.  Krause  and  Meinicke  seem  to  imagine  that  the  experi- 
ments on  rabbits  reported  in  my  first  paper  formed  the  basis  of  my  state- 
ment that  ■•  the  Krause-Meinicke  experiments  allow  of  an  interpretation 
other  than  that  given  by  the  authors."'  But  in  my  second  paper,  the  one 
attacked  by  Krause  and  Meinicke,  it  will  be  seen  that  I  injected  the  virus 
of  three  cases  of  human  poliomyelitis  and  of  five  cases  of  experimental 
poliomyelitis  in  monkeys  into  rabbits  without  any  positive  result;  the  virus 
from  all  these  cases,  injected  into  monkeys,  immediately  caused  disease 
and  death.  These  are  the  experiments  I  have  described  in  full  above ; 
in  my  second  paper,  owing  to  the  entirely  negative  character  of  the  results, 
I  did  not  feel  justified  in  burdening  the  reader  with  the  full  details.  In 
their  first  paper  Krause  and  Meinicke  made  the  general  statement  that 
rabbits  are  susceptible  to  the  virus  of  poliomyelitis,  without  specifying 
any  conditions  as  to  age  or  variety  of  the  rabbits  used.  If  they  object 
to  my  experiments  on  this  score  it  can  be  only  because  they  overlook  the 
fact  that  they  set  up  such  standards  at  a  later  date.  There  is  only  one 
point  to  which  perhaps  I  have  not  given  sufficient  attention  and  which  might 
make  the  criticism  of  Krause  and  Meinicke  justifiable.  In  their  first  paper 
they  state  that  ':  very  large  doses  were  used."'  Unfortunately,  no  indication 
is  given  as  to  what  doses  they  regard  as  being  i:  very  large."'  Later  they 
rejected  the  intracerebral  method  of  injection  because  it  did  not  allow  of 
large  doses  being  administered ;  but  the  reports  in  their  first  paper  con- 
tradict the  necessity  for  this  course,  because  in  them  they  state  that  they 
succeeded  in  infecting  rabbits  by  just  this  method. 

Results  obtained  by  other  Observers. — Very  competent 
observers,  such  as  Flexner  and  Lewis,  Leiner  and  v.  Wiesner. 
Landsteiner  and  Levaditi,  have  obtained  entirely  negative  results 
with  virus  which  promptly  produced  paralysis  in  monkeys.  At  a 
later  date  Eichelberg",  Selter,  and  Potpeschnigg  all  failed  to  produce 
the  disease  by  injection  of  lumbar  puncture  fluid.  However, 
Krause  and  Meinicke  make  the  further  accusation  against  me,  that 
I  have  not  paid  enough  attention  to  the  reports  of  positive  results; 
they  quote  in  this  connection  the  experiments  of  Bonhoff,  Beneke, 
and  Dahm. 

Bonhoff  reported  that  three  rabbits  died  twenty-two  days  after  inocu- 
lation with  material  from  a  case  of  human  poliomyelitis,  but  that  none  of 
them  showed  any  microscopical  lesions  characteristic  of  poliomyelitis,  nor 
did  material  obtained  from  the  brain,  spinal  cord,  and  spleen  of  these 
animals  affect  other  rabbits  in  any  way.     He  concludes  :      "  I  cannot  trace 


74  EPIDEMIC  INFANTILE  PARALYSIS 

the  cause  of  death  in  these  animals.  They  were  well  nourished,  and  suffered 
from  no  injuries.  I  agree  with  my  colleague,  Romer,  that  no  symptoms 
such  as  those  described  by  Krause  and  Meinicke  appeared  in  our  animals; 
in  particular,  no  paralysis  occurred."  I  do  not  think  that  this  statement 
by  Bonhoff  contained  anything  which  could  justly  cause  me  to  change  my 
opinion  of  the  results  obtained  by  Krause  and  Meinicke.  The  experiments 
of  Beneke  would  have  been  more  likely  to  do  so.  He  injected  three  rabbits 
with  material  containing  the  virus  of  poliomyelitis,  and  observed  peculiar 
symptoms  ending  in  the  death  of  the  animals ;  but  the  spinal  cords  were 
found  to  be  free  from  any  demonstrable  pathological  change.  Considering 
that  I  used  the  same  material  as  Bonhoff  and  Beneke  for  an  extensive  series 
of  experiments  on  monkeys  and  rabbits,  and  that  I  did  not  observe  the 
death  of  one  single  rabbit  in  circumstances  which  were  in  any  way  sus- 
picious, I  was  unable  to  accept  the  observations  of  Beneke  and  Bonhoff  as 
in  any  way  proving  that  rabbits  were  susceptible  to  the  virus  of  poliomyelitis. 
I  may  add  that  these  authors  themselves  do  not  agree  that  their  results  can 
be  considered  to  constitute  a  proof  of  the  transmissibility  of  the  disease  to 
rabbits,  as  Krause  and  Meinicke  have  tried  to  make  out. 

The  observations  of  Dahm  are  of  but  little  value,  as  they  do  not  include 
any  microscopical  examination  of  the  material. 

In  the  same  papers  Krause  and  Meinicke  quote  Kraus  and 
Levaditi  in  support  of  their  argument.  They  state  that  the  experi- 
ments of  the  latter  constitute  a  "  confirmation  and  completion  "  of 
their  own. 

Kraus  at  first  was  unable  to  obtain  any  positive  result  with  intra- 
cerebral injection  of  pm.  virus  into  rabbits ;  later,  he  saw  one  animal  die 
with  symptoms  like  those  of  rabies;  the  medulla  and  brain  of  this  rabbit 
injected,  into  other  young  rabbits  produced  symptoms  of  disease.  He  draws 
the  conclusion  that  "  these  experiments,  which  will  be  carried  further,  show 
that  transmission  of  the  disease  to  young  rabbits  is  possible."  Krause  accen- 
tuates the  fact  that  "  the  lesions  characteristic  of  poliomyelitis  were  not 
found  in  these  animals."  Later,  Krause  again  became  very  sceptical  about 
the  value  to  be  attached  to  experiments  with  rabbits.  At  the  meeting  of 
the  Freien  Vereinigung  fur  Mikrobiologie,  held  in  Berlin  in  1910,  he  stated 
that  all  attempts  to  transmit  the  disease  from  the  "infected"  rabbits  to 
monkeys  had  failed.  He  again  called  attention  to  the  fact  that  the  result 
of  microscopical  examination  was  entirely  negative,  and  said  that  the  whole 
question  of  the  transmission  of  the  disease  to  rabbits  was  not  proven,  and 
that  all  apparently  successful  inoculations  should  be  received  with 
scepticism. 

The  experiments  of  Landsteiner  and  Levaditi  can  be  accepted  still  less 
as  constituting  a  "  confirmation  and  completion  "  of  those  of  Krause  and 
Meinicke.  The  former  report  that  in  all  attempts  save  one  they  failed  to 
obtain  any  result ;  this  particular  rabbit  received  an  intracerebral  injection 
on  December  2Q,  igog,  of  virus  which  had  been  passed  through  a  monkey; 
twenty-four  days  later  the  animal  died  without  showing  any  signs  of 
paralysis.  On  microscopical  examination  appearances  were  seen  which 
were  similar  to  those  observed  in  human  poliomyelitis.  The  perivascular 
infiltration,  so  typical  in  human  and  monkey  poliomyelitis,  was  but  little 
marked.  Landsteiner  and  Levaditi  give  it  as  their  opinion  that  in  this  one 
case  there  was  an  affection  of  the  central  nervous  system,  similar  to  that 
observed  in  poliomyelitis  in  man  and  the  monkey.      How  far  removed  they 


ETIOLOGY   OF  THE   DISEASE  75 

were  from  admitting  that  rabbits  are  suitable  subjects  for  the  investigation 
of  poliomyelitis,  or  that  the  experiments  of  Krause  and  Meinicke  are  of  any 
value  in  proving  this,  is  shown  by  the  exhaustive  criticism  to  which  they 
subject  this  theory  in  their  latest  work  (November,  iqio).  We  shall  return 
to  this  matter  later.  Landsteiner  and  Levaditi  say  cautiously  that  the  trans- 
mission appears  to  have  been  successful  in  this  case.  But  the  proof  is  by  no 
means  complete,  as  no  successful  inoculations  into  other  animals,  specially 
monkeys,  were  made  from  this  case.  I  suggest  further,  in  view  of  the  fact 
that  this  case  of  Landsteiner  and  Levaditi  is  the  only  one  in  which  lesions 
in  any  way  resembling  poliomyelitis  have  been  seen,  that  it  is  not  impos- 
sible that  they  were  due  to  a  spontaneous  disease  in  the  rabbit  and  not  to 
the  experimental  inoculation.  Joest  and  Degen  have  proved  the  existence 
of  the  epidemic  Borna's  disease  in  horses,  and  it  is  quite  possible  that  a 
similar  disease  occurs  in  rabbits. 

So  far,  none  of  the  results  obtained  by  other  authors  can  be 
regarded  as  confirming'  those  recorded  by  Krause  and  Meinicke. 
The  experiments  made  by  Lentz  and  Huntemuller  at  the  Institute 
for  Infectious  Diseases  in  Berlin  are  more  to  the  point. 

Lentz  and  Huntemuller  received  from  Krause  and  Meinicke  in  Hagen 
rabbits  and  monkeys  which  had  been  inoculated  with  the  cerebrospinal 
fluid,  brain  and  spinal  cord,  spleen  and  blood  of  patients  who  had  died  of 
infantile  paralysis.  They  report  that  most  of  the  rabbits  died  after  a  shorter 
or  longer  period,  generally  seven  to  eleven  days,  but  sometimes  two 
months  (!)  afterwards;  rabbits  and  monkeys  were  inoculated  successfully 
with  various  organs  from  these  animals.  Lentz  and  Huntemuller  believe 
that  the  symptoms  were  due  to  the  poliomyelitis  virus  received  in  Hagen. 
Krause  and  Meinicke,  in  their  most  recent  paper,  formulate  the  conditions 
under  which  a  successful  result  with  rabbits  may  be  expected.     These  are  :■ — 

(i)  Only  particular  varieties  of  rabbits  must  be  used;  Krause  and 
Meinicke  describe  these  more  closely. 

(2)  Only  young  rabbits  of  not  excessive  body  weight  are  susceptible. 

(3)  Only  rabbits  which  have  received  "  large  doses  "  show  signs  of  the 
disease.  (Unfortunately,  in  this  their  latest  paper  these  authors  omit  to 
state  what  they  mean  by  "  large  doses."  If  this  point  is  really  of  so  much 
importance,  it  is  essential  in  our  opinion  that  some  data  should  be  given 
respecting  the  weight  of  fluid,  blood,  or  emulsion  used.) 

Renewed  Repetition  of  the  Experiments. — In  view  of  the  new 
conditions  laid  down  by  Krause  and  Meinicke,  and  of  the  results 
obtained  by  Lentz  and  Huntemuller,  I  felt  that  a  new  situation 
had  arisen.  In  collaboration  with  Joseph  I  carried  out  a  new  series 
of  experiments  in  order  to  settle  the  question  of  the  utility  of 
rabbits  in  this  field  of  research. 

As  the  criticism  of  Krause  and  Meinicke  was  directed  solely  against 
myself,  I  asked  Dr.  Joseph  to  form  his  judgment  as  to  the  suitability  of  the 
rabbit  for  experiment  quite  independently ;  in  this  way  I  hoped  to  obtain 
an  unbiased  opinion.  Dr.  Joseph  made  the  following  experiments  inde- 
pendently of  me;  we  also  observed  the  animals  apart  from  one  another. 
The  conditions  under  which  the  experiments  were  carried  out  were  those 
described  as  the  most  favourable  by  Krause  and  Meinicke  :  Belgian  giant- 
rabbits  of  unobjectionable,  well-attested  pedigree,  chosen  by  an  experienced 
breeder    of    rabbits,     were    used    exclusively;    only    young    animals    were 


76  EPIDEMIC   INFANTILE   PARALYSIS 

employed  which  we  had  watched  growing  up  ourselves ;  the  weight  of  the 
animals  used  varied  from  400  gm.  to  710  gm.,  an  average  of  600  gm.  ;  the 
method  of  inoculation  was  that  recommended  by  Krause  and  Meinicke  as  the 
most  certain,  viz.  :  simultaneous  intraperitoneal  and  intravenous  injection. 
Contrary  to  Krause  and  Meinicke,  we  made  an  attempt  to  measure  the  dose 
given ;  it  was  weighed  in  the  moist  state  before  injection.  The  material 
used  was  an  emulsion  of  the  brain  and  spinal  cord  of  a  monkey  which  had 
died  of  typical  poliomyelitis. 

Experiment  11,  April  27,  1910. — The  virus  used  was  an  emulsion  of  the 
brain  and  spinal  cord  of  monkey  42  (virus  No.  12  passed  through  four 
monkeys).  Four  Belgian  giant-rabbits  (946,  947,  948,  and  949)  weighing 
from  460  gm.  to  630  gm.  each  received  2  c.c.  of  5  per  cent,  emulsion 
filtered  through  paper  intravenously,  and  3  c.c.  of  the  same  emulsion  un- 
filtered  into  the  peritoneum.  On  the  same  day  monkey  49  [Macacus  rhesus) 
received  an  intracerebral  injection  of  '6  c.c.  of  the  same  virus. 

Result  :  Monkey  49  well  until  May  9.  On  the  10th  paresis  of  the  hind 
limbs,  right  more  than  left ;  this  became  worse  during  the  next  days. 
Improvement  began  on  the  13th,  but  there  was  well-marked  paralysis  for  a 
long  time.     Later  the  animal  got  quite  well. 

Rabbits  946,  947  and  948  remained  well  for  four  months,  during  which 
time  they  were  observed  daily.  Rabbit  949  became  paralysed  in  the  left 
fore  limb  and  left  hind  limb  on  May  14;  the  paralysis  varied  in  degree 
and  was  permanent.  It  affected  only  the  limbs  of  the  left  side,  and  was 
definitely  spastic  in  character,  e.g.,  the  left  hind  limb  can  scarcely  be  bent 
at  all.  The  animal  was  killed  on  June  21  for  purposes  of  diagnosis. 
Macroscopic  investigation  was  negative. 

Dr.  Joseph  took  the  trouble  to  make  serial  sections  of  the  spinal  cord 
and  of  pieces  of  the  medulla  and  brain.  No  lesions  characteristic  of  polio- 
myelitis could  be  found  in  this  animal.  Unfortunately,  he  did  not  succeed 
in  finding  any  cause  for  the  paralysis.  We  have  never  observed  a  spastic 
hemiplegia  in  monkeys,  nor  has  Wickman  throughout  his  wide  experience 
in  man,  and  it  is  probably  not  incorrect  to  assume  that  the  paralysis  in  this 
rabbit  was  not  due  to  the  injection,  or,  at  any  rate,  was  not  the  result  of 
infection  with  poliomyelitis.  I  may  mention  here  that  paralysis  is  observed 
very  frequently  in  rabbits  kept  in  hutches  in  the  laboratory,  and  that  the 
cause  cannot  be  found   always. 


Experiment  12,  May  19,  1910. — An  emulsion  of  the  brain  and  spinal 
cord  of  monkey  48  (virus  No.  11,  passed  through  six  monkeys)  was  used. 
Rabbits  943,  944,  945,  950,  951,  and  952  received  an  intravenous  injection 
of  2  c.c.  of  a  5  per  cent,  emulsion  filtered  through  paper,  also  an  intra- 
peritoneal injection  of  3  c.c.  of  the  same  virus  unfiltered.  Monkey  56 
received  '8  c.c.  of  the  emulsion  into  the  brain  and  3  c.c.  into  the  peritoneum. 

All  the  rabbits  remained  perfectly  well,  without  a  trace  of  paralysis, 
during  four  months  under  daily  observation. 

Monkey  56  remained  well  until  June  1.  On  June  2  in  the  morning 
paresis  of  the  fore  limbs ;  in  the  afternoon  definite  paresis  t»f  the  hind  limbs ; 
June  3  paresis  more  marked;  June  4  total  paralysis  of  the  left  hind  limb 
and  of  the  right  fore  limb,  marked  paresis  of  the  other  limbs;  June  5-7, 
condition  unchanged;  June  8,  marked  general  paralysis.  Found  dead  on 
the    10th.     Typical  microscopical  appearances. 


ETIOLOGY   OF  THE   DISEASE  77 

Experiment  13,  May  31,  1910. — An  emulsion  of  the  brain  and  spinal 
cord  of  monkey  36  (virus  No.  11  passed  through  five  monkeys)  was  used. 

Inoculation  was  carried  out  with  rabbits  953,  954,  956,  957,  958,  959,  960, 
961,  962,  963,  and  with  monkey  58.  The  rabbits  received  an  intraperitoneal 
injection  of  2  c.c.  of  a  5  per  cent,  filtered  emulsion  and  an  intravenous 
injection  of  3  c.c.  unfiltered  emulsion.  Monkey  58  received  '5  c.c.  of  filtered 
virus  into  the  brain. 

All  the  rabbits  remained  well  for  four  months  under  daily  observation. 

Monkey  58  remained  well  until  June  10.  On  the  nth  total  paralysis 
of  the  left  hind  limb  and  paresis  of  the  right  hind  limb.  On  the  12th  total 
paralysis  of  both  hind  limbs  and  paresis  of  both  fore  limbs.  On  the  13th 
general  paralysis  and  death.  Microscopical  appearances  very  typical  and 
very  intense  in  the  lumbar  region. 


Experiment  14,  July  13,  1910. — The  virus  used  was  an  emulsion  of  the 
brain  and  cord  of  monkey  48  (Virus  No.  n  passed  through  six  monkeys). 
Rabbits  964,  965,  966,  967,  968,  969,  970,  971,  972,  973,  and  monkey  102  were 
inoculated.  The  rabbits  received  an  intravenous  injection  of  2  c.c.  of  a 
5  per  cent,  emulsion  filtered  through  paper,  and  an  intraperitoneal  injection 
of  3  c.c.  of  the  s  per  cent,  emulsion  unfiltered. 

All  the  rabbits  remained  well  for  four  months  under  daily  observation. 

Monkey  102  received  an  intracerebral  injection  of  '6  c.c.  of  5  per  cent, 
emulsion,  unfiltered.  Well  until  the  24th.  On  the  25th  typical  flaccid 
paresis  of  the  hind  limbs  and  weakness  of  the  back  muscles.  In  the  even- 
ing paralysis  of  the  hind  limbs  and  of  the  left  fore  limb,  facial  palsy  on 
the  right  side.     Death  on  the  25th.     Microscopical  appearances  typical. 

Thirty-one  rabbits  in  four  series  received  large  doses  of 
material  containing  the  virus  of  poliomyelitis  by  simultaneous 
intravenous  and  intraperitoneal  injection.  The  virulence  of  the 
material  used  was  proved  by  the  fate  of  the  four  control  monkeys, 
which  all  died  of  typical  poliomyelitis.  Of  the  thirty-one  rabbits, 
thirty  remained  well  for  four  months  under  daily  observation;  one 
single  animal  suffered  from  an  atypical  form  of  paralysis  for  which 
no  lesion  of  the  nature  of  poliomyelitis  could  be  made  responsible. 

This  closes  the  series  of  our  experiments  with  rabbits.  In  all, 
including  the  earlier  experiments,  there  were  eighty-one  animals; 
of  these,  one  died  from  suppuration  following  a  bite,  two  died  of 
pleuropneumonia,  one  of  a  cause  unknown,  and  one  of  a  form  of 
paralysis  not  due  to  poliomyelitis,  but  the  cause  of  which  could 
not  be  elucidated.     All  the  rest  remained  well. 

Even  when  we  conformed  to  all  the  conditions  laid  down  by 
Krause  and  Meinicke,  we  were  unable  to  corroborate  their  results. 
Our  observations  form  a  complete  contrast  to  those  obtained  by 
Krause  and  Meinicke,  as  also  by  Lentz  and  Huntemiiller.  As  I 
do  not  believe  that  the  matter  can  be  carried  any  further  by  means 
of  experiment,  I  will  attempt  to  do  so  by  a  critical  discussion  of 
the  facts. 

Criticism  of  the  Arguments  in  Favour  of  using  Rabbits. — 
Krause  and  Meinicke  base  their  view,  that  the  rabbit  is  a  suitable 


78  EPIDEMIC   INFANTILE   PARALYSIS 

animal  for  experiments  with  poliomyelitis  and  that  their  results 
prove  this,  upon  the  following"  arguments :  They  emphasize  the 
facts  (1)  that  rabbits  inoculated  at  the  same  time  become  ill  at  the 
same  time  and  some  time  after  the  infection;  (2)  that,  consequently, 
the  symptoms  observed  cannot  be  due  directly  to  injury  received 
at  the  time  of  injection,  owing  to  material  from  another  animal 
being  introduced  into  the  blood;  (3)  that  the  symptoms  observed 
were  certainly  "nervous  in  character."  This  argument  is  not 
quite  sound;  I  refer  the  reader  to  the  full  description  of  my  earlier 
experiments  (pp.  30-31);  there  he  will  find  that  the  introduction 
of  morbid  material  of  various  kinds  (streptococci,  B.  coll)  in  fact 
of  any  foreign  substance  in  a  molecular  state  directly  into  the 
blood-stream,  will  cause  paralysis  or  symptoms  similar  to  paralysis 
at  a  time  considerably  later  than  the  date  of  injection. 

Lately  Selter  has  again  found  that  infection  of  rabbits  with 
streptococci  causes  paralysis.  In  this  connection  the  researches  of 
Potpeschnigg  are  even  more  instructive.  He  obtained  a  diplo- 
coccus  from  the  cerebrospinal  fluid  of  a  case  of  poliomyelitis,  and 
injected  living  and  dead  cultures  of  this  organism  into  the  peri- 
toneum, veins,  and  brains  of  rabbits.  "In  a  few  cases  widespread 
paralysis  resulted."  This  author  was  prevented  from  drawing  a 
wrong  conclusion  from  his  results  by  a  knowledge  of  previous 
experiments  with  rabbits  (cf.  p.  31).  In  view  of  the  present  dis- 
cussion I  recommend  the  reader  to  refer  again  to  these  experiments. 

In  addition,  Lentz  and  Huntemuller,  who  believe  that  they 
have  confirmed  the  results  obtained  by  Krause  and  Meinicke,  have 
stated :  "  We  would  not  lay  much  stress  upon  convulsions  and 
paralysis  occurring  in  rabbits;  we  have  observed  rabbits  which  died 
of  convulsions  soon  after  being  brought  to  the  department  and 
by  inoculation  from  these  animals  zve  have  occasionally  been  able 
to  produce  convulsions  in  others."* 

Meinicke's  further  argument,  that  no  other  cause  of  death  was 
ascertainable,  is  of  very  little  value;  how  often  do  we  not  have 
to  put  a  query  under  the  heading  "  Cause  of  death,"  in  the  case 
of  rabbits  which  die  in  the  laboratory?  One  of  the  best  arguments 
in  support  of  their  contention  would  have  been  the  demonstration 
that  the  lesions  produced  in  their  rabbits  were  similar  to  the  lesions 
of  poliomyelitis  in  man  or  monkey.  Indeed,  In  the  course  of  a 
lecture  before  the  Rheinisch-Westfalischen  Gesellschaft  fur  innere 
Medizin  und  Nervenheilkunde,  on  November  14,  1909,  Meinicke 
said:  "Together  with  Dr.  Holm,  of  Essen,  we  were  able  to 
demonstrate  qualitatively  the  same  changes  in  one  of  our  rabbits, 
which  died  with  characteristic  symptoms,  as  are  found  in  typical 
cases  of  poliomyelitis  in  man  and  in  monkeys.  Vascular  and  diffuse 
cell  infiltrations  and  small  haemorrhages  were  found  in  the  grey 
matter  of  the  spinal  cord  and  degenerative  change  in  the  tigroid 
of  the  ganglion  cells."  In  another  place  he  says:  "It  may  be 
mentioned  here  that  we  found  characteristic  changes  (thrombosis, 

*  No  italics  in  the  original. 


ETIOLOGY   OF  THE   DISEASE  79 

nsemorrhage,  diffuse  and  perivascular  cell  infiltration)  in  the  central 
nervous  system  of  animals  inoculated  from  these  rabbits."  Finally, 
he  said:  "Thus  the  final  proof  is  provided;  we  were  justified  in 
interpreting"  our  results  with  rabbits  as  a  true  transmission  of  the 
virus  of  infantile  paralysis.'"' 

But  the  experiments  of  Lentz  and  Huntemuller,  which  he  him- 
self quotes  in  support  of  his  argument,  are  not  in  keeping"  with 
this  generalization.  These  authors  write :  "  Microscopical  evid- 
ence of  any  lesion  is  frequently  very  slight,  but  congestion  of  the 
vessels,  haemorrhages  and  cell  degeneration  are  often  to  be  found 
in  the  grey  matter,  particularly  of  the  brain.  We  were  unable  to 
find  any  cell  infiltration  round  the  vessels  or  in  the  substance  of 
the  central  nervous  system  such  as  is  found  in  cases  of  poliomyelitis 
in  man  and  in  monkeys."* 

Lentz  and  Huntemuller  make  a  definite  statement,  therefore, 
that  they  did  not  find  perivascular  infiltration  as  was  observed  by 
Meinicke.  But  we  shall  see  later  that  perivascular  infiltration  is 
the  most  characteristic  change  in  poliomyelitis.  With  regard  to 
the  findings  of  Lentz  and  Huntemuller,  I  must  call  attention  again 
to  the  results  of  the  earlier  experiments  in  which  not  only  bacteria 
of  all  kinds  but  also  non-living  material  was  used.  The  changes 
described  by  the  former  experimenters  remind  one  forcibly  of  those 
found  by  Lentz  and  Huntemuller.  Personally,  I  found  myself  un- 
able to  agree  that  their  specimens,  which  were  demonstrated  at  a 
meeting  of  the  Freien  Vereinigung  fiir  Mikrobiologie,  showed  the 
presence  of  the  lesions  of  poliomyelitis.  Landsteiner  said  of  these 
specimens:  "The  preparations  from  rabbits  which  have  been 
demonstrated  show  very  slight  changes;  in  the  sections  of  the 
spinal  cord  of  a  monkey  inoculated  with  material  from  a  rabbit 
by  Lentz  and  Huntemuller  there  are  none  of  those  characteristic 
changes  which  are  always  found  in  monkeys,  and  I  do  not  think  that 
a  diagnosis  of  poliomyelitis  should  be  made,  nor  do  I  think  it  a 
probable  diagnosis.  I  have  seen  similar  appearances  in  animals 
which  certainly  did  not  die  of  poliomyelitis." 

As  there  can  be  no  doubt  that  the  monkey  is  susceptible  to 
the  virus  of  poliomyelitis,  and  as  the  disease  can  be  reproduced 
in  monkeys  in  a  form  both  clinically  and  pathologically  similar  to 
the  disease  in  man,  the  question  whether  the  rabbits  of  Krause  and 
Meinicke  and  of  Lentz  and  Huntemuller  really  died  of  the  effects 
of  poliomyelitis  virus  allows  of  a  crucial  experiment.  If  the  rabbits 
died  of  poliomyelitis,  inoculation  of  a  monkey  with  material  obtained 
from  them  should  produce  the  typical  clinical  and  pathological 
picture  of  poliomyelitis  in  the  susceptible  monkey.  Krause  and 
Meinicke  claim  to  have  carried  out  this  experiment  and  Lentz  and 
Huntemuller  in  Berlin  set  up  the  same  claim.  We  will  consider 
these  claims  more  closely. 

I  have  collected  the  allegedly  convincing  experiments  from  Meinicke's 
papers,  and  arranged  them  in  the  form  of  a  genealogy. 

*  No  italics  in  the  original. 


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EPIDEMIC   INFANTILE   PARALYSIS 


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ETIOLOGY   OF  THE   DISEASE  8 1 

We  must  confess  to  having"  many  doubts  as  to  the  validity 
of  the  proof  put  forward.  In  the  first  place,  it  is  remarkable 
that  lumbar  puncture  fluid  should  be  the  original  virus-containing 
material,  and  that  at  a  date  several  days  after  the  beginning  of 
the  paralysis.  As  we  shall  see  later,  in  no  single  instance  has  it 
been  found  possible  to  infect  monkeys  with  human  cerebrospinal 
fluid.  It  would  be  very  remarkable  if  such  material  had  affected 
a  rabbit,  which  is  at  least  less  susceptible  than  a  monkey.  Further, 
the  first  rabbits  only  became  ill  after  thirty-five  days  (the  one 
which  was  sent  to  Berlin  only  after  fifty  days),  while  the  subsequent 
rabbits  (275-278)  died  in  four  to  five  days.  I  can  hardly  believe 
that  the  fact  that  these  animals  were  younger  can  account  for  such 
a  difference  in  incubation  period.  The  symptoms  observed  in  the 
monkeys  were  not  in  any  way  typical  of  poliomyelitis.  I  must 
refer  the  reader  to  Meinicke's  original  publication  on  this  point;  he 
says  himself  that  he  did  not  observe  any  marked  paralysis  in  the 
monkeys.* 

Landsteiner  says  of  the  observations  made  by  Meinicke  :  "  It 
is  quite  uncertain  from  what  disease  these  monkeys  suffered.''  In 
another  place,  in  conjunction  with  Levaditi,  he  says:  "  Elles  sont 
peu  nettes  et  ne  sauraient  etre  idendifiees  a  celles  que  Ton  releve 
ordinairement  chez  l'homme,  ou  les  simiens  infectes  avec  du  virus 
de  passage." 

The  Berlin  experiments  quoted  by  Krause  and  Meinicke  show  clearly 
that  these  authors  accept  a  small  amount  of  evidence  as  proof  that  polio- 
myelitis has  been  transmitted  to  monkeys.  In  these  experiments  the  blood 
of  a  monkey  alleged  to  be  suffering  from  poliomyelitis  was  said  to  have 
caused  abortive  poliomyelitis.  One  of  the  monkeys  inoculated  showed 
"  transient  nervous  symptoms  "  after  a  week  had  elapsed,  and  Krause  and 
Meinicke  actually  say  that  "  this  experiment  gives  valuable  support  to  our 
own  inoculations  with  the  blood  of  rabbits  and  human  beings." 

How  little  the  symptoms  observed  in  Meinicke's  monkeys  had  to  do 
with  poliomyelitis  is  shown  further  by  the  observation  made  by  him,  that 
acutely  and  severely  paralysed  cases  were  able  to  overcome  the  paralysis 
occasionally,  when  they  were  stimulated  to  perform  movements  and  were 
subjected  to  radiant  heat.  Such  an  observation  has  never  been  made  by 
any  other  investigator  of  poliomyelitis.  When  Meinicke  goes  so  far  as  to 
explain  the  atypical  character  of  the  disease  produced  by  suggesting  that 
the  action  of  the  virus  on  monkeys  has  been  altered  by  its  passage  through 
rabbits  he  is  ignoring  the  -petitio  -princifiii. 

*  He  certainly  continues  :  "  On  further  careful  study  of  the  results 
reported  by  Romer,  I  have  received  the  impression  that  they  more  or  less 
correspond  with  symptoms  observed  in  my  monkeys."  But  I  must  object 
strongly  to  the  view  that  the  symptoms  observed  by  me  bore  the  remotest 
resemblance  to  those  described  by  Meinicke.  I  hope  that  the  full  report 
of  the  symptoms  which  I  have  given  above  will  enable  the  reader  to  form 
his  own  judgment.  Let  him  compare  them  with  those  described  by  Meinicke 
in  the  Deutsche  med.  Wochenschrift,  1910,  15,  and  see  whether  the  latter 
bear  any  resemblance  to  the  symptoms  I  have  described,  and  which  Meinicke 
himself  demonstrated  by  means  of  the  cinematograph  at  the  Medical 
Congress  at  Wiesbaden  in   1910. 


82  EPIDEMIC   INFANTILE   PARALYSIS 

In  the  Berlin  experiments  of  Lentz  and  Huntemuller,  which  are  quoted 
as  confirmatory,  monkeys  inoculated  with  human  cerebrospinal  fluid  died 
seven  to  eleven  days  after  infection  "  without  having  shown  any  signs  of 
paralysis."  "  Pathological,  microscopical,  and  bacteriological  examination 
proved  negative."  The  transmission  of  the  disease  from  rabbits,  sent  from 
Hagen  to  Berlin,  to  monkeys  was  successful.  The  monkeys  showed 
"  repeated  short  periods  of  paralysis  at  intervals  of  two  to  four  weeks." 
Another  monkey  "  died  of  marasmus  following  two  attacks,  from  which 
it  had  recovered  partially."  Yet  another  was  "  killed  during  an  attack." 
In  these  monkeys  were  found  "  marked  engorgement  of  the  vessels, 
haemorrhages,  degeneration  of  the  ganglion  cells,  which  were  invaded  by 
small  cell  infiltration,"  i.e.,  no  adventitial  or  perivascular  infiltration,  the 
characteristic  lesion  of  the  disease. 

It  is  clear  that  in  these  experiments  neither  true  paralysis  nor 
characteristic  microscopical  lesions  were  observed.  Lentz  and 
Huntemuller  assume  that  the  virus  was  attenuated  in  order  to 
explain  this.  The  difference  between  my  results  and  those  of  the 
Hagen  and  Berlin  investigators  cannot  be  bridged.  I  found  that 
material  which  was  fully  virulent  in  monkeys  was  non-virulent  in 
rabbits,  and  yet  in  Hagen  and  Berlin  material  which  was  feebly 
virulent  or  non-virulent  for  monkeys  was  virulent  for  rabbits  The 
question  of  a  biological  change  having  taken  place  in  the  virus  might 
have  been  considered  if  I  and  other  writers  had  not  obtained  similar 
results  by  using  virus  taken  direct  from  human  beings.  The  fact 
that  Lentz  and  Huntemuller  were  able  to  infect  rabbits  easily  with 
virus  sent  to  them  by  Landsteiner  from  Vienna  and  by  me  from 
Marburg,  while  we  found  the  same  virus  entirely  non-virulent  for 
rabbits,  still  remains  to  be  cleared  up.  I  shall  return  to  the  question 
of  how  these  contradictions  may  be  explained. 

So  far,  the  results  of  a  critical  analysis  prove  that  Krause  and 
Meinicke  are  not  justified  in  claiming  that  their  results  prove  that 
rabbits  are  susceptible  to  the  virus  of  poliomyelitis  and,  therefore, 
that  they  are  suitable  animals  for  research,  nor  that  they  had  suc- 
ceeded in  transmitting  the  disease  to  rabbits.  A  number  of  im- 
portant considerations  still  remain. 

Further  Objections  to  Experiments  with  Rabbits. — To  begin 
with,  it  is  remarkable  that  the  intracerebral  method  should  have 
proved  less  efficacious  than  the  intraperitoneal  and  intravenous 
methods.  Experiments  with  monkeys  have  proved  the  intracerebral 
method  to  be  the  most  certain.  Considering  the  selective  affinity 
-of  the  virus  to  the  central  nervous  system,  it  is  difficult  to  under- 
stand why  bringing  virus  and  the  central  nervous  system  directly 
together  should  have  given  such  poor  results.  Further,  it  is  really 
extraordinary  that,  besides  the  brain  and  spinal  cord,  the  lumbar 
puncture  fluid,  the  spleen  pulp,  and  the  blood  of-human  beings,  and 
the  liver  of  a  monkey  should  all  prove  to  contain  the  virus.  Even 
by  using  the  very  susceptible  monkey,  no  other  experimenter  has 
succeeded  in  demonstrating  the  virus  in  this  material.  I  myself  had 
consistently  negative   results   when  using  blood   and   cerebrospinal 


ETIOLOGY   OF  THE   DISEASE  83 

fluid  direct  from  man  to  monkey,  and  Flexner  and  Lewis,  Leiner 
and  v.  Wiesner,  Landsteiner  and  Levaditi  have  all  had  the  same 
experience.  Selter  and  Potpeschnigg  injected  cerebrospinal  fluid 
without  result.  Only  Flexner  and  Lewis  have  been  able  to  find 
virus  in  the  blood  and  cerebrospinal  fluid  of  monkeys,  and  then  only 
by  using  enormous  quantities  of  blood  and  under  special  conditions 
with  cerebrospinal  fluid  (intracerebral  injection  of  the  monkey  with 
removal  of  the  cerebrospinal  fluid  before  the  occurrence  of  para- 
lysis). 

The  experience  of  Lentz  and  Huntemuller  relative  to  the 
resistance  of  the  virus  to  glycerine  is  totally  different  to  my  own. 
They  state  that  preservation  in  50  per  cent,  glycerine  diminishes 
the  virulence;  that  they  succeeded  in  inoculating"  only  one  out  of 
four  monkeys  with  the  virus  which  I  sent  to  them  does  not  alter  the 
fact  that  in  my  experiments  the  glycerine  virus  was  transmitted 
readily  from  monkey  to  monkey,  and  led  to  a  typical  illness  in  90 
per  cent,  of  the  cases. 

Bearing  in  mind  all  the  objections,  the  uncertainty  of  the 
clinical  symptoms  and  the  absence  of  any  typical  microscopical 
change,  one  can  only  be  very  surprised  that  Krause  and  Meinicke 
believe  that  their  opinion,  that  the  inoculation  with  material  con- 
taining pm.  virus  was  the  cause  of  death  in  their  rabbits,  "  has  been 
confirmed  in  all  directions." 

To  recapitulate  :  the  following  facts  justify  the  scepticism  with 
which  numerous  authors  have  looked  upon  rabbits  as  subjects  for 
experimental  poliomyelitis  and  have  regarded  the  interpretation 
which  Krause  and  Meinicke  have  placed  upon  their  results.  The 
symptoms  observed  in  rabbits  are  of  no  value.  The  alleged  positive 
results  were  obtained  with  material  which  was  proved  not  to  con- 
tain the  virus  in  an  infective  condition,  because  it  failed  to  produce 
poliomyelitis  even  in  such  a  sensitive  animal  as  the  monkey.  The 
experimentum  cruris  must  be  considered  to  have  failed  since  reinfec- 
tion from  the  rabbit  back  to  the  monkey  did  not  produce  poliomye- 
litis in  the  latter.  The  histological  lesions  found  in  the  rabbits 
correspond  to  lesions  which  are  easily  produced  whenever  any 
foreign  material  is  injected  into  rabbits,  and  they  are  quite  different 
to  the  lesions  of  poliomyelitis.  The  alleged  positive  results 
obtained  by  Krause  and  Meinicke,  Lentz  and  Huntemuller  are 
opposed  by  the  at  least  equally  numerous  negative  results  obtained 
by  a  larger  number  of  observers,  who  worked  with  highly  virulent 
material  and  in  part  under  the  optimum  conditions  as  formulated 
by  Krause  and  Meinicke.  No  support  is  given  by  any  investigations 
along  the  lines  of  serum-diagnosis  {vide  infra). 

An  Attempt  to  explain  the  Difference. — It  is  naturally  very 
difficult  to  elucidate  the  cause  of  death  in  the  rabbits  observed  by 
Krause  and  Meinicke  and  Lentz  and  Huntemuller.  The  following 
is  a  possible  explanation  :  It  is  possible  that  the  animals  suffered 
from  some  other  disease,  which  was  inoculable  from  one  to  the 
other  and  was   carried   by  a  non-bacterial   virus.        The   difference 


84  EPIDEMIC  INFANTILE   PARALYSIS 

between  the  results  obtained  by  Lentz  and  Huntemiiller  on  the  one 
hand,  and  Joseph  and  myself  on  the  other,  using  the  same  virus, 
would  seem  to  point  to  this.  In  Berlin  the  virus  from  Marburg 
produced  the  same  results  in  rabbits  as  that  from  Hagen;  in  our 
hands,  under  the  most  favourable  conditions  and  with  rabbits  which 
were  said  to  be  of  the  most  susceptible  variety,  the  virus  proved 
itself  innocuous  to  rabbits.  One  sentence  in  the  paper  by  Lentz 
and  Huntemiiller  is  also  significant;  they  say  that  rabbits  which 
had  not  been  injected  and  had  only  just  arrived  at  the  laboratory 
sometimes  suffered  from  convulsions,  and  that  inoculations  made 
from  these  animals  into  others  caused  convulsions.  We  cannot  say 
if  this  explanation  is  the  true  one,  and  I  agree  with  the  position 
taken  up  by  Landsteiner  and  Levaditi :  "  que  les  divergences  doivent 
dependre  de  quelques  circonstances  encore  mal  definies  a  l'heure 
actuelle." 

Practical  Conclusions. — Krause  and  Meinicke,  by  making 
claims  to  which  they  have  no  right,  make  it  necessary  that  the  whole 
position  of  the  rabbit  should  be  clearly  defined  even  at  the  risk  of 
fatiguing  the  reader.  Krause  and  Meinicke  make  no  less  a  claim 
than  this:  "That  these  experiments  prove  for  the  first  time  that 
acute  epidemic  infantile  paralysis  is  a  communicable  disease."  In 
another  place:  "  The  proof,  furnished  by  us  for  the  first  time,  that 
the  virus  of  poliomyelitis  can  be  cultivated  for  a  considerable  time 
within  the  bodies  of  animals  has  made  it  possible  to  determine  the 
nature  of  the  virus  more  exactly,  to  test  the  efficacy  of  therapeutic 
measures  by  means  of  experiments  with  animals,  and,  above  all,  to 
study  the  question  of  immunity  in  animals."  They  claim  further 
that  they  are  the  first  to  demonstrate  the  capacity  of  the  virus  to 
pass  through  a  filter.  I  hope  that  I  have  proved  conclusively  that 
there  is  no  justification  for  such  claims. 

A  more  important  reason  than  this  question  of  priority  arises 
from  the  nature  of  the  practical  deductions  drawn  by  Krause  and 
Meinicke.  In  our  opinion  they  are  not  justified.  They  recom- 
mend the  rabbit  for  testing  for  the  presence  of  poliomyelitis  virus 
in  faeces,  in  urine,  in  mucus  from  the  throat,  and  in  articles  of 
food.  They  advise  inoculation  into  rabbits  for  diagnostic  purposes 
in  doubtful  cases,  even  in  the  abortive  type  of  poliomyelitis.  They 
hope  to  arrive  at  a  diagnosis  by  injecting  the  blood  of  a  doubtful 
case  during  life  into  a  rabbit.  A  grave  practical  danger  is  present 
in  these  recommendations;  the  rabbit  is  so  sensitive  to  all  kinds 
of  trauma  and  disease,  and  reliable  criteria,  by  which  a  positive 
result  may  be  judged,  are  so  few  that  serious  mistakes  are  inevit- 
able. 

One  more  assertion  by  Krause  and  Meinjcke  requires  correc- 
tion. They  say:  "A  comparison  of  our  results  with  rabbits  and 
those  obtained  by  other  writers  with  monkeys  seems  to  show  that 
the  rabbit  is  at  least  as  susceptible  as  the  monkey,  and  perhaps 
more  so."  In  another  place  they  speak  of  "  the  relatively  great 
susceptibility  of  the  rabbit,"   in  which   "  relative  "   can  apply  only 


ETIOLOGY  OF  THE  DISEASE  85 

to  the  monkey,  the  only  other  animal  which  enters  into  the  question. 
The  facts  are  the  following" :  90  to  95  per  cent,  of  monkeys  which 
receive  an  intracerebral  injection  of  the  virus  become  affected  with 
poliomyelitis,  and  most  of  them  die  of  the  disease;  in  my  own 
experience  and  that  of  most  other  authors  not  one  single  rabbit 
contracted  poliomyelitis,  and  a  critical  examination  of  alleged  posi- 
tive results  makes  it  clear,  that  at  any  rate  it  is  very  improbable 
that  the  symptoms  observed  can  be  connected  with  the  virus  in  any 
way. 

On  one  point  one  can  agree  with  Krause  and  Meinicke.  They 
point  out  that  monkeys  are  not  suitable  for  the  study  of  conditions 
of  immunity,  because  large  series  of  these  animals  are  not  possible 
for  obvious  reasons.  Unfortunately  a  knowledge  of  this  fact  does 
not  render  other  unsuitable  animals  any  more  suitable  for  the 
purpose. 

Krause  and  Meinicke  have  underestimated  the  importance  of 
the  experiments  made  with  monkeys;  they  clearly  do  not  realize 
how  susceptible  the  monkey  is  and  how  typical  are  the  clinical  and 
pathological  features  which  are  produced.  The  number  of  experi- 
ments which  can  be  carried  out  with  monkeys  by  each  individual 
investigator  must  remain  small;  but  when  we  are  in  a  position,  as 
at  the  present  time,  to  collect  the  results  of  experiments  performed 
all  over  the  world  (New  York,  Paris,  Vienna,  Marburg),  results 
may  be  obtained,  as  we  have  seen  already  and  shall  see  later,  which 
are  of  the  greatest  importance  to  science.  With  rabbits  the  most 
experienced  investigators — Flexner  and  LeAvis,  Landsteiner  and 
Levaditi,  Leiner  and  v.  Wiesner,  and  many  others — have  obtained 
only  the  most  dubious  results. 

So  far  the  rabbit  has  not  proved  to  be  a  suitable  animal  for  the 
investigation  of  poliomyelitis. 

[Since  Professor  Romer  thus  defined  the  position  of  the  rabbit 
as  an  animal  for  experiment,  the  American  investigator,  H.  K. 
Marks,  has  carried  out  further  experiments.  Using  virus  obtained 
from  the  brain  and  spinal  cord  of  a  monkey  affected  with  poliomye- 
litis he  made  intravenous  and  intraperitoneal  injections  into  rabbits; 
the  animals  died  on  the  eighth  to  fifteenth  day  with  convulsions. 
Post-mortem  examination  revealed  no  lesions,  but  the  disease  was 
able  to  be  transmitted  to  further  rabbits  by  injection  of  the  brain  and 
spinal  cord  in  most  cases,  and  sometimes  by  using  the  liver  and 
spleen.  Marks  was  unable  to  carry  the  disease  through  more  than 
six  rabbits  in  this  manner.  From  the  second,  fourth,  and  sixth  - 
rabbit-passages,  however,  he  was  able  to  produce  typical  lesions  of 
poliomyelitis  in  three  monkeys  by  intracerebral  inoculation  with  the 
brain  and  spinal  cord  of  the  respective  rabbits.  Marks  says 
definitely  that  in  the  rabbits  "  the  disease  cannot  be  recognized  as 
poliomyelitis";  further,  he  claims  only  to  have  demonstrated  that 
"  the  disease  can  survive  and  probably  even  be  propagated  in  a 
domestic  animal  that  does  not  show  any  of  the  peculiar  symptoms 


86  EPIDEMIC   INFANTILE  PARALYSIS 

of  the  disease  as  it  occurs  in  man."  From  this  it  is  clear  that  his 
experiments  do  not  give  any  support  to  the  claims  made  on  behalf 
of  the  rabbit  by  Krause  and  Meinicke.  It  is  true  that  the  results 
of  re-inoculation  from  the  diseased  rabbits  into  monkeys  proved  the 
presence  in  them  of  the  virus  of  poliomyelitis,  but  until  the  monkey 
was  employed  there  was  no  evidence  that  the  virus  of  poliomyelitis 
was  present  in  the  rabbits.  The  position  of  the  rabbit  thus  remains 
the  same  as  when  it  was  defined  by  Professor  Romer. — Trans.] 


CHAPTER  IV. 

Pathology  and  Pathogenesis. 


I.— HISTORICAL   RETROSPECT— THE    SALIENT 

FEATURES. 

Heine's  Views. — In  my  opinion  a  retrospect  of  the  pathology 
of  the  disease  should  begin  with  a  man  whose  name  is  not  often 
heard  in  this  connection.  Heine  in  his  first  monograph  mentioned 
the  spinal  cord  as  the  probable  seat  of  the  lesion  involved,  and  in 
his  second  monograph  he  insisted  upon  the  spinal  nature  of  the 
disease.  In  order  to  do  full  justice  to  Heine's  clear  and  definite 
statement  it  is  necessary  to  remember  that  before  him  no  one  had 
studied  the  disease  in  a  scientific  manner,  and  also  what  the  condi- 
tion of  neuropathology  was  at  that  time.  It  is  true  that  Heine  did 
not  demonstrate  the  lesion  which  he  postulated,  but  that  does  not 
detract  from  the  value  of  his  discovery.  He  himself  regretted  that 
he  could  produce  only  hypotheses  and  not  facts  in  the  matter  of 
the  pathogenesis  of  the  disease.  The  arguments  by  which  he  estab- 
lished his  thesis  were  so  exact  and  so  comprehensive,  that  I  feel 
impelled  to  draw  attention  to  this  portion  of  his  services  to 
medicine. 

He  first  excludes  the  brain  as  the  seat  of  the  disease  and,  by 
a  process  of  clear,  logical  criticism,  arrives  at  the  spinal  cord  as 
the  site  of  the  cause  of  the  paralysis.  "  Although  the  primary  irri- 
tative signs  mentioned  above  do  not  exclude  the  possibility  of  a 
lesion  of  the  nerve  centres,  and  although  one  cannot  be  sure  that 
some  of  the  symptoms  observed  during  the  acute  period  are  not 
due  to  an  irritative  lesion  of  the  brain,  yet  the  subsequent  signs 
point  rather  to  a  lesion  of  the  spinal  cord  as  the  essential  factor  in 
producing  the  paralysis,  without  more  than  a  transient  affection  of 
the  brain  and  its  functions.  The  disease  may  consist  in  a  sudden 
pressure  on  the  cord  produced  by  capillary  extravasations  or  other 
exudates,  which  would  lead  to  atrophy  later,  or  there  may  be  some 
other  kind  of  lesion."  A  contemporary  statement  of  Bardeleben's 
shows  how  much  Heine's  view  appealed  to  clinicians  :  "  Against 
the  cerebral,  and  in  favour  of  the  spinal  localization  of  the  lesion, 
the    following    facts    are    of    importance :     the    absence    of    lasting 


88  EPIDEMIC  INFANTILE  PARALYSIS 

cerebral  signs;  the  integrity  of  the  organs  of  special  sense  and  of 
the  intellect;  finally,  the  rapid  loss  of  electrical  excitability  in  the 
muscles.  It  is  well  known  that  in  paralysis  due  to  a  cerebral  lesion 
the  electrical  excitability  is  maintained  for  years,  while  the  spinal 
cord  in  this  respect  behaves  like  a  nerve,  and  a  lesion  of  it  causes 
disappearance  of  the  reaction  in  the  muscles  in  two  or  three  weeks." 

Heine  was  undoubtedly  wise  in  rejecting  rickets,  scrofula,  and 
syphilis  as  being  of  any  pathogenic  importance.  His  firmness  in 
adhering  to  his  view  of  the  spinal  nature  of  the  disease  was  of  great 
value  when  the  celebrated  French  clinicians,  Rilliet  and  Barthez, 
published  negative  results  from  autopsies  and  gave  the  name  of 
"  essential  paralysis  "  to  the  disease.  And  again,  when  Bouchut 
considered  the  disease  to  be  a  "  paralysis  idiopathica  "  caused  by 
cold.  Bardeleben  criticized  the  negative  findings  of  the  former  two 
authors  with  the  words  :  "  They  are  of  but  little  value  owing  to  the 
exclusively  macroscopical  nature  of  the  investigation." 

Heine's  reasons  for  assuming  a  lesion  of  the  cord  were  the 
following:  The  functions  of  the  brain  are  not  affected;  the  paralysis 
succeeds  the  general  symptoms  immediately,  which  would  not  be 
the  case  if  the  lesion  were  peripheral;  the  loss  of  electrical  excita- 
bility, the  absence  of  sensory  symptoms.,  the  degree  of  paralysis, 
the  frequency  with  which  the  paralysis  affects  the  lower  limbs,  the 
subsequent  muscular  atrophy,  the  incurability  of  the  paralysis  are  all 
points  against  a  peripheral  localization.  The  occurrence  of  similar 
paraplegia  in  lesions  due  to  other  diseases  affecting  the  spinal  cord 
led  Heine  directly  to  a  spinal  localization.  Finally,  and  this  reveals 
the  born  clinician  in  Heine,  he  was  convinced  by  the  appearance  of 
the  helpless  patients  that  he  had  to  deal  with  a  deep-seated  lesion 
of  the  nervous  system.  He  drew  attention  especially  to  the  grey 
matter  of  the  cord  as  "  the  chief  channel  of  motor  activity."  With 
a  prophetic  insight  into  the  true  nature  of  the  pathogenesis  he  adds  : 
"  Knowing  all  this,  knowing  that  the  grey  matter  is  so  well  sup- 
plied with  blood-vessels  that  accidental  plethora  may  easily  cause 
extravasations,  while  the  grey  matter  is  exceedingly  liable  to  suffer 
from  variations  in  its  nutriment,  knowing  that  the  sections  show 
atrophy  of  the  grey  matter  to  be  the  cause  of  the  paralysis,  what  is 
to  hinder  us  from  deducing  the  cause  of  the  diminution  of  motility 
from  the  same  factors  ?  Why  should  we  not  suppose  some  acute 
process  to  take  place,  which  causes  an  alteration  in  the  grey  matter, 
impairs  its  conductivity,  produces  the  paralysis  in  the  lower  limbs, 
and,  by  affecting  the  nutrition  of  the  grey  matter,  causes  secondary 
atrophy  in  it?"  In  another  place:  "Although  the  preceding 
anatomical  facts  and  my  experimental  experience  lead  me  to  consider 
the  various  types  of  paralysis  as  due  to  spinal  lesions,  and  being,  in 
a  way,  different  degrees  of  the  same  disease,  I  must  not  be  under- 
stood to  set  apart  particular  portions  of  the  cord  as  the  invariable 
seat  of  the  primary  infection  nor  to  consider  any  particular  kind  of 
lesion  as  pathognomonic;  in  the  present  state  of  our  knowledge  of 
the    physiology    and    pathological    anatomy   of    the    part    I    cannot 


PATHOLOGY    AND    PATHOGENESIS  Sq 

make  more  than  conjectures.  Yet  I  cannot  but  give  expression  to 
my  firm  conviction  that  it  is  not  in  the  brain  or  in  the  peripheral 
nerves,  but  in  the  spinal  cord  itself,  speaking  generally,  that  we 
must  seek  the  cause  of  infantile  paralysis.  Even  although  we 
possessed  no  anatomical  proof,  yet  the  uniformity  of  the  symptoms 
in  150  carefully  observed  cases,  all  pointing  to  this  organ,  is  of  no 
small  importance;  a  theory  based  on  observation  of  so  large  a 
number  of  cases  might  even  venture  to  fill  the  gaps  left  in  our 
knowledge  of  the  pathology.  I  would  ask  those  who  are  not 
satisfied  with  the  results  of  pathological  research  (I  myself,  con- 
scious as  I  am  of  their  incompleteness,  cannot  regard  them  as  being 
a  final  proof),  whether  they  are  able  to  bring  forward  other  facts 
in  support  of  their  own  different  opinions  or  to  formulate  any  theory 
which  will  hold  as  good  in  all  the  circumstances.  If  such  people, 
who  are  only  too  prone  to  give  the  name  '  essential  infantile  para- 
lysis '  to  our  disease,  because  it  avoids  the  difficulty  of  specifying 
the  nature  of  the  illness,  bring  to  me  sections  which  show  no  lesion 
of  the  nerve  centres,  I  would  advise  them  to  use  the  microscope ;  if 
this  also  fails  to  reveal  a  lesion  I  would  suggest  that,  if  at  the 
present  time  changes  are  not  evident  to  our  eye,  it  is  the  latter 
which  is  at  fault. 

"  Although  I  cannot  but  emphasize  my  conviction  that  it  is  the 
spinal  cord  which  is  involved,  yet  it  remains  only  my  humble 
opinion.  I  shall  be  quite  satisfied  if  my  statement  has  the  practical 
result  of  stimulating  the  interest  of  physicians  in  the  disease,  so  that 
the  number  of  pathological  investigations  may  increase  and  thereby 
a  definite  result  be  attained. 

"  On  consideration  of  all  the  factors,  and  with  the  concurrence 
of  many  authors,  I  have  adopted  the  name  paralysis  infantilis 
spinalis  for  this  form  of  paralysis;  with  all  respect  to  the  authority 
of  Rilliet  in  matters  pertaining  to  diseases  of  children,  I  consider 
his  term  '  paralysie  essentielle  '  which  has  been  so  widely  adopted, 
as  also  that  of  Bouchut,  '  paralysis  idiopathica,'  to  be  incorrect." 

It  is  not  going  too  far  to  say  that  it  was  Heine  who  showed  the 
way  for  all  subsequent  research;  he  indicated  the  spinal  cord  as  the 
seat  of  the  disease,  and  in  so  far  he  was  the  founder  of  the  patho- 
genesis of  the  disease. 

From  Heine  to  Charcot,  Roger  and  Damaschino. — The  post- 
mortem reports  published  by  Heine  included  some  cases  of  paralysis 
due  to  other  diseases ;  in  one  case  (Longet,  "  Anatomie  et  Physiolog'ie 
du  Systeme  nerveux, "  Part  I)  there  was  paralytic  club-foot,  marked 
atrophy  of  the  anterior  roots  and  the  corresponding  lumbar  and 
sacral  nerves,  but  no  abnormality  of  the  spinal  cord.  Another  case 
(Hutin)  was  certainly  one  of  old  infantile  paralysis;  in  this  there 
was  an  extraordinary  atrophy  of  the  spinal  cord.  This  was  the  first 
positive  post-mortem,  although  the  findings  were  only  macroscopic. 

The  Frenchman  Cornil  (1863)  made  the  first  thorough  micro- 
scopical examination  of  a  case  (a  woman,  aged  49,  who  had  suffered 
from  the  effects   of  infantile  paralysis  for  forty-seven  years).     He 


go  EPIDEMIC   INFANTILE  PARALYSIS 

found  considerable  atrophy  of  the  ventrolateral  column,  particularly 
in  the  dorsal  and  lumbar  regions,  amyloid  bodies  in  the  anterior 
horns,  most  numerous  in  the  vicinity  of  the  blood-vessels.  Cornil 
passed  by  the  most  important  change,  although  he  not  only  observed 
it  but  also  described  and  illustrated  it:  "On  voit  une  cellule  ner- 
veuse,  qui  est  du  reste  la  settle  qui  montrait  cette  preparation; 
mais  stir  les  coupes  plus  epaisses  nous  avons  vu  que  les  cellules  ner- 
veuses  etaient  intactes  et  avaient  conserve  leurs  rapports  normaux.'' 
Cornil  therefore  observed  the  absence  of  ganglion  cells,  but  did  not 
lay  any  stress  upon  it.  His  discovery  was  confirmed  by  Laborde  in 
1864,  who  examined  two  cases  and  found  inflammatory  connective 
tissue  in  the  anterior  and  lateral  tracts,  but  noted  that  the  ganglion 
cells  were  "  parfaitement  saines." 

In  1865  Prevost  and  Vulpian  went  distinctly  further;  they  noted 
atrophy  of  the  anterior  horns  and  diminution  in  the  number  of 
ganglion  cells,  as  well  as  atrophy  of  the  anterior  and  lateral 
columns.  Lockhart  Clark  confirmed  this  in  1868.  These  authors 
therefore  observed  the  most  important  fact  and  described  it,  but 
did  not  appreciate  that  it  was  the  one  thing  by  which  the  occurrence 
of  the  paralysis  could  be  explained. 

This  was  reserved  for  a  work  which  on  that  account  may  be 
considered  as  laying  the  true  foundation  of  all  subsequent  micro- 
scopical pathology.  Charcot  and  Joffroy,  in  1870,  made  an  examina- 
tion of  a  woman  aged  40,  who  had  been  paralysed  for  thirty-three 
years;  they  found  similar  appearances  as  the  authors  mentioned 
above,  but  they  recognized  the  fundamental  pathological  importance 
of  the  loss  of  the  ganglion  cells,  and  formulated  the  brilliant  hypo- 
thesis that  the  ganglion  cells  form  a  kind  of  trophic  centre  for  the 
nerves  and  muscles  belonging  to  them;  this  theory  made  it  possible 
to  understand  the  occurrence  of  the  paralysis,  and  the  subsequent 
muscular  atrophy.  The  investigations  of  Charcot  and  Joffroy  are 
important,  not  only  because  of  this  generally  accepted  neuro- 
physiological  theory,  but  because  of  the  further  conclusions  which 
they  drew.  On  account  of  the  remarkable  way  in  which  certain 
groups  of  cells,  markedly  in  the  lumbar  enlargement,  were  chiefly 
affected,  and  in  view  of  the  absence  of  any  true  inflammatory  or 
haemorrhagic  changes,  they  inferred  a  primary  affection  of  the 
ganglion  cells  with  the  production  of  a  certain  degree  of  secondary 
reaction  in  the  neighbouring  interstitial  tissues. 

Charcot's  and  Joffroy 's  observations  were  confirmed  in  the 
same  year  by  Parrot  and  Joffroy,  who  accepted  the  theoretical  con- 
clusions of  the  former.  But  one  further  discovery  was  made  which 
was  to  be  of  great  importance  for  the  further  development  of  the 
subject.  In  a  child  aged  3,  one  year  after  it  had  been  afflicted  with 
poliomyelitis,  they  found  blood-vessels  which  were  more  numerous, 
thickened,  and  infiltrated  with  small  round  cells  in  situations  where 
the  ganglion  cells  appeared  normal.  As,  however,  they  found 
ganglion  cells  affected  in  other  places  without  any  particular  change 
in  the  blood-vessels  being  present,  they  adhered  to  the  theory  of 


PATHOLOGY    AND    PATHOGENESIS  9 1 

Charcot.  In  the  next  year  (1871)  Roger  and  Damaschino  were 
able  to  demonstrate  marked  changes  in  the  vessels,  with  cell  pro- 
liferation in  the  anterior  horns  in  more  recent  cases  (i.e.,  after  two 
and  a  half,  six,  and  thirteen  months).  They  raised  the  question, 
without  giving  any  decisive  answer,  whether  the  process  was 
primarily  parenchymatous,  as  Charcot  believed,  or  primarily  inter- 
stitial. 

In  any  case  these  investigations  excluded  the  possibility  that 
the  process  was  a  purely  degenerative  one;  it  was  undoubtedly  an 
inflammatory,    "myelitic"   process. 

The  Dispute  over  Charcot's  Theory. — The  discussion  appears 
at  first  sight  to  be  tiresomely  academic.  Wickman  points  out  that 
it  is  not  so,  because  the  assumption  of  a  primary  interstitial  inflam- 
mation at  once  raises  the  difficulty  as  to  how  the  "systematic" 
character  of  the  symptom-complex  in  most  of  the  cases  can  be 
explained. 

(a)  Investigation  of  Chronic  Cases. — Discussion  was  limited  at 
first  to  the  results  obtained  by  examination  of  cases  of  long  stand- 
ing. Roth  confirmed  the  findings  of  Roger  and  Damaschino,  but 
came  to  the  conclusion  that  the  interstitial  changes  were  primary 
and  the  degeneration  of  the  ganglion  cells  secondary.  Schultze  in 
1875  pointed  out  that  frequently  only  isolated  groups  of  cells  were 
affected,  and  he  considered  that  this  would  not  be  possible  if  the 
pathological  process  was  primarily  parenchymatous.  Other  oppo- 
nents of  Charcot's  theory  were  Erb,  Leyden  (1875).  Turner  (1879), 
Taylor  (1879),  Eisenlohr  (1880),  Archambault  and  Damaschino 
(1883).  who  drew  attention  to  the  frequent  occurrence  of  peri- 
vascular cell  infiltration,  and  conceived  the  whole  process  to  be  one 
of  diffuse  myelitis  with  a  tendency  to  greater  intensity  in  particular 
regions.  Eisenlohr  observed  further  that  the  posterior  horns  and 
the  white  matter  were  also  affected.  Kawka  (1889)  proved  the 
connection  between  the  localized  lesions  and  the  changes  in  the 
vessels  by  means  of  serial  sections.  Jagic,  Hoche.  van  Gehuchten, 
Bielschowsky,  and  others  opposed  Charcot's  theory  as  a  result  of 
investigation  of  chronic  cases. 

On  the  other  hand,  supporters  of  Charcot  appeared,  Dejerine 
(1878),  Stadelmann  (1883),  and.  m  particular,  von  Kahlden  in  1893 
and  1 901,  who  examined  five  chronic  cases,  and  gave  it  as  his 
opinion  that  the  interstitial  changes  present  did  not  need  any  theory 
of  a  primary  interstitial  affection  for  their  explanation.  His  point 
of  view  was  certainly  influenced,  if  not  determined,  by  his  theory  of 
the  nature  of  inflammation  in  general ;  in  common  with  YVeigert  he 
regarded  all  inflammation  in  a  parenchymatous  organ  as  primarily 
parenchymatous  in  nature.  Other  authors  adopted  a  middle  view 
between  the  two  extremes.  Schmaus.  Schwalbe,  Lovegren,  and 
Praetorius  pointed  out  the  possibility  of  simultaneous  affection  of 
both  the  parenchymatous  and  interstitial  elements,  and  laid  stress 
on  the  difficulty  of  solving  the  problem  along  morphological  lines. 

As    a    result    of    these    studies    the    important    conclusion    was 


92  EPIDEMIC   INFANTILE   PARALYSIS 

arrived  at,  that  the  same  process  occurs  in  adults  as  in  children ; 
Combault  in  1873  substantiated  the  theory  of  Duchenne  that  a  spinal 
paralysis  of  adults  exists,  analogous  to  the  spinal  paralysis  of 
children. 

(b)  Investigation  of  Acute  Gases. — The  problem  had  not 
reached  solution  by  means  of  examination  of  chronic  cases;  more 
was  to  be  hoped  of  examination  of  acute  cases. 

We  owe  the  first  comprehensive  and  thorough  investigations  to 
Rissler.  In  three  acute  cases  he  found  interstitial  change  as  well 
as  degeneration  of  the  ganglion  cells;  although  the  stroma  was 
markedly  affected  he  contended  that  the  cells  were  primarily 
affected  because:  "  The  pathological  changes  in  the  neighbourhood 
of  the  cells  were  neither  so  constant  nor  sufficient  to  be  considered 
to  be  the  cause  or  even  a  contributory  cause  of  the  cell  degenera- 
tion." He  bases  his  argument  largely  upon  one  case,  in  which 
cell  degeneration  was  very  marked,  while  interstitial  changes  were 
but  slight.  Rissler  admitted  the  possibility  that  the  morbid  agent 
might  have  an  effect  upon  the  walls  of  the  blood-vessels  as  well. 
He  was  the  first  to  prove  that  the  pia  was  involved  by  the  disease. 
Leegaard  (1889),  Gowers  (1892),  and  Monckeberg  (1903)  agreed  with 
Rissler's  view.  Monckeberg  found  poliomyelitis  acutissima  in  a 
case  of  Landry's  paralysis.  He  indicated  one  difficulty  inherent  in 
the  theory  that  the  localization  of  the  disease  depends  upon  the 
distribution  of  the  blood-vessels:  "How  is  one  to  understand  the 
special  liability  to  disease  of  certain  regions,  particularly  the  central 
portions  of  the  cord  in  poliomyelitis?"  He  considers  the  theory 
of  Goldscheider  not  a  very  happy  one:  "That  the  vessels  in  that 
region  have  certain  peculiarities  in  their  walls,  and  that  the  condi- 
tions of  pressure  of  the  stroma  are  different  to  those  in  other  por- 
tions." Monckeberg  agrees  with  Weigert's  view  that  there  is 
primary  damage  to  the  ganglion  cells  with  secondary  change  in 
the  vessel  walls,  rendering  them  more  permeable  to  leucocytes. 
"  In  poliomyelitis  we  find  the  typical  picture  of  inflammation  in  a 
parenchymatous  organ."  In  quite  recent  times  (191 1)  Cassirer  has 
given  his  adherence  to  the  theory  of  primary  involvement  of  the 
ganglion  cells. 

At  the  same  time  it  is  impossible  not  to  realize  that  the  more 
Investigation  of  acute  cases  has  been  carried  out  the  more  opinion 
has  inclined  towards  a  primary  interstitial,  vascular  process.  Cer- 
tain investigators,  Dauber  (1893-94 — a  five  days'  case),  Redlich 
(1894 — a  ten  days'  case),  Medin  (1898),  Neurath  (1905 — a  three 
days'  case),  leave  the  question  an  open  one  and  prefer  to  suppose  a 
simultaneous  affection  of  both  parenchyma  and  interstitial  tissue. 
But  most  investigators  adopt  the  "  interstitial  "  theory.  Gold- 
scheider (1893 — a  twelve  days'  case)  was  particularly  impressed  by 
the  intensity  of  the  vascular  change,  and  goes  so  far  as  to  state  that 
the  localization  of  the  disease  is  determined  by  the  vascular  changes. 
He  draws  attention  to  the  manner  in  which  the  central  artery  is 
affected  (with  reference  to  Kadyis's  work),  and  holds  that  the  cell 


PATHOLOGY    AND    PATHOGENESIS  93 

degeneration  is  secondary  and  due  to  nutritional  disturbance. 
Siemerling  (1894 — an  eight  days'  case)  also  regards  the  vascular 
changes  as  the  essential  feature.  Similar  views  were  expressed 
subsequently  by  Bickel  and  Roder  (1898),  Biilow-Hansen  and 
Harbitz  (1899),  Matthes  (1899),  Placzek  (1901),  Marinesco  (1901), 
and  Batten  (1904). 

Wickman's  Investigations. — The  work  of  Wickman  (1905)  was 
of  extreme  importance  not  only  because  of  its  extent  (seven  acute 
cases,  three  of  Rissler's  cases  re-examined,  and  two  cases  during 
Convalescence)  and  its  thoroughness  and  clearness  of  description, 
but  also  because  of  the  expert  critical  analysis  of  all  the  vexed 
points  in  the  pathology  and  pathogenesis  of  the  disease  which  it 
contains.  He  raised  the  questions,  really  for  the  first  time,  of  the 
point  of  entrance,  the  method  of  infection  and  of  spread  of  the  virus. 
The  conclusions  drawn  from  his  exhaustive  studies  are  extremely 
valuable.  In  1910  he  amplified  them  by  the  study  of  seven  more 
acute  cases. 

In  the  following  I  shall  not  give  Wickman's  results  in  detail. 
I  propose  to  compare  the  results  I  obtained  by  microscopical 
examination  of  cases  of  experimental  poliomyelitis  in  monkeys  in 
each  case  with  those  obtained  by  research  in  man;  I  shall  refer 
mainly  to  the  investigations  of  Wickman  in  this  connection  because 
his  descriptions  are  so  clear  and  his  illustrations  so  excellent  that 
is  is  easy  for  the  layman  in  microscopic  pathology,  as  I  must  con- 
sider myself  to  be,  to  arrive  at  a  clear  understanding  of  his  mean- 
ing. The  following  is  a  short  sketch  of  the  more  important 
theoretical  conclusions  arrived  at  by  Wickman. 

The  symptoms  of  poliomyelitis  acuta  of  both  adults  and 
children  (the  lesions  are  the  same  in  both)  are  due  to  an  inflamma- 
tory process  in  the  central  nervous  system.  This  process  is  not 
limited  to  the  spinal  cord,  but  occurs  in  a  disseminated  form  in  the 
medulla,  pons,  cerebellum,  cerebrum,  and  meninges.  It  is  essen- 
tially therefore  a  disseminated  meningo-myelo-encephalitis.  Not 
only  the  anterior  horns,  nor  even  the  grey  matter  in  general,  but 
also  the  white  matter  and  the  pia  mater  are  affected;  the  process  is 
usually  most  intense  in  the  anterior  horns  in  the  cervical  and  lum- 
bar enlargements.  The  variation  in  the  intensity  of  the  process  is 
dependent  upon  the  varying  richness  of  blood  supply  to  the  parts. 
Both  parenchymatous  and  interstitial  changes  are  found;  the  latter 
are  particularly  well  marked.  Changes  in  the  ganglion  cells  are 
never  found  in  the  absence  of  interstitial  lesions,  but  the  opposite 
condition  is  present  sometimes.  The  process  therefore  is  mainly 
interstitial  and  of  the  infiltrative,  lymphocytic  type.  The  infiltra- 
tion mainly  follows  the  distribution  of  the  blood-vessels.  Inflam- 
matory oedema  also  plays  some  part  in  the  pathology. 

Within  the  nervous  system  the  inflammation  travels  along  the 
perivascular  lymphatics ;  the  perineural  lymphatics  probably  carry 
the  infection  from  the  site  of  inoculation  to  the  spinal  cord.  The 
alimentary  tract   is   probably  the   site    of   infection   in   most   cases, 


94  EPIDEMIC   INFANTILE   PARALYSIS 

because,  clinically,  intestinal  symptoms  are  common,  and  the  para- 
lysis usually  begins  in  the  lower  limbs. 

As  a  side  issue  it  is  important  to  note  that  Wickman  established 
the  identity  of  Landry's  paralysis  and  certain  forms  of  myelitis 
with  poliomyelitis.  These  investigations  into  the  microscopic 
pathology  of  the  disease  formed  the  basis  of  his  later  clinical  studies 
and  enabled  him  to  obtain  a  comprehensive  view  of  these  diseases, 
which  differ  so  much  in  their  symptomatology  and  yet  are  probably 
identical  in  their  etiology.  His  well-deserved  clinical  discoveries 
were  the  ripe  fruit  of  his  careful  pathological  studies. 

More  Recent  investigators. — These  have  been  numerous  since 
Wickman  (Forssner  and  Sjovall,  Harbitz  and  Scheel,  Barnes  and 
Miller,  Kadwalader,  Marburg,  Hoffmann,  Hochhaus,  Bauer, 
Strauss,  Benecke,  Pirie,  Marchand).  The  results  of  Harbitz  and 
Scheel  are  important  both  because  their  material  was  extensive 
(thirteen  cases)  and  because  they  differ  from  Wickman  on  one  point. 
They  consider  that  the  infection  is  carried  to  the  central  nervous 
system  by  the  blood  as  well  as  by  the  lymph-stream;  the  vessels  of 
the  meninges  are  attacked  first,  and  the  infection  then  follows  the 
vessels  into  the  substance  of  the  cord.  Forssner  and  Sjovall  lay 
stress  on  the  role  played  by  phagocytes  in  the  destruction  of  the 
ganglion  cells,  and  Wickman,  who  paid  little  attention  to  this  point 
in  his  earlier  works,  recognizes  its  importance  in  his  later  ones. 
These  two  authors  have  the  credit  of  being  the  first  to  describe 
the  affection  of  the  spinal  ganglia,  which  discovery  has  been  con- 
firmed by  Marburg,  Strauss,  Harbitz  and  Scheel,  and  Bauer.  In 
his  latest  work  Wickman  has  described  round  cell  infiltration  in  the 
subpericardial  fat. 

These  are  the  results  so  far  of  investigation  by  methods  of 
microscopic  pathology.  Now  that  it  is  possible  to  produce  experi- 
mentally a  symptom  complex  in  monkeys  similar  to  that  which 
occurs  in  man,  we  may  hope  that  the  doubtful  points  will  be 
cleared  up.  The  problems  of  the  pathogenesis  of  the  disease 
are :  — 

(i)  Where  is  the  most  common  point  of  entry  of  the  virus? 

(2)  Along  what  route  does  the  virus  reach  the  brain  and  spinal 
cord? 

(3)  How  does  its  further  distribution  within  the  central  nervous 
system  take  place  ? 

(4)  What  point  in  the  central  nervous  system  is  first  affected  ? 

II— THE  DISTRIBUTION  AND  SPREAD  OF  THE 
VIRUS  WITHIN  THE  ORGANISM. 

The  Demonstration  of  the  Virus  in  Different  Organs. — It  is  of 

primary  importance,  if  the  above  questions  are  to  be  solved,  to 
know  where  in  the  body  the  virus  may  be  found.  As  the  virus  is 
so  stable,  we  may  assume  that  the  distribution  of  it  which  is  found 
in  the  cadaver  holds  good  for  the  living  body.     In  the  next  place 


PATHOLOGY    AND    PATHOGENESIS  95 

it  is  necessary  to  distinguish  between  the  distribution  found  in  man 
and  that  found  in  the  monkey;  in  the  latter  the  disease  has  been 
produced  only  experimentally  by  methods  which  we  know  do  not 
correspond  to  the  natural  method  of  infection  for  the  most  part, 
or  which  we  know  to  be  but  imperfect  imitations.  So  far,  the  only 
way  to  prove  the  existence  of  the  virus  has  been  by  means  of  experi- 
ments with  monkeys,  and  the  method  of  intracerebral  injection  has 
shown  itself  to  be  the  most  certain  in  its  effects. 

(a)  In  Man. — As  has  been  shown  in  the  chapter  on  the  etiology, 
the  virus  was  first  proved  to  be  present  in  the  spinal  cord  of  persons 
dead  of  Heine-Medin  disease,  as  was  to  be  expected  a  priori.  The 
virus  has  also  been  found  in  the  brain,  specially  in  the  cortex ; 
whether  it  is  always  present  in  this  situation,  even  when  the  clinical 
symptoms  are  purely  spinal  in  character,  cannot  be  stated  definitely. 

All  attempts  to  demonstrate  the  virus  in  the  cerebrospinal  fluid 
have  failed;  this  is  extremely  unfortunate  as  its  presence  would 
have  been  an  important  aid  to  diagnosis.  I  have  injected  fluid  from 
two  severe  acute  cases  into  monkeys;  one  of  the  cases  was  in  the 
earliest  paralytic  stage.  Flexner  and  Lewis  have  had  equally  nega- 
tive results;  in  1907  they  gave  intracerebral  and  intraperitoneal 
injections  to  monkeys  without  any  result.  The  experience  of 
Leiner  and  v.  Wiesner,  Strauss  and  Huntoon,  Netter,  Potpeschnigg 
and  Selter  has  been  similar.  Experiments  with  the  blood  of  persons 
actually  ill  with  poliomyelitis  or  dead  of  the  disease  have  had  the 
same  negative  result. 

Owing  to  the  analogy  which  exists  between  poliomyelitis  and 
rabies  I  thought  of  the  possibility  that  the  virus  might  be  found  in 
the  salivary  glands.  I  therefore  gave  intracerebral  injections  to 
monkeys  of  emulsions  of  the  parotid  gland  and  pancreas  of  a  case 
which  had  died  during-  the  acute  stage  of  the  disease;  the  result  was 
negative.  The  virus  was  present  in  the  central  nervous  system  of 
this  case  in  a  fully  virulent  form  (cf.  p.  41).  In  order  to  test  the 
excretion  of  the  virus  I  filtered  the  saliva  of  several  children,  after 
having-  diluted  it  with  saline,  through  a  Berkefeld  filter;  intra- 
cerebral injection  of  the  filtrate  into  monkeys  produced  no  effect. 

The  virus  has  been  found  in  only  one  situation  outside  the 
central  nervous  system  in  man.  Flexner  and  Lewis  proved  it  to  be 
present  in  the  mesenteric  glands  of  a  child  which  had  died  of  acute 
poliomyelitis;  the  injection  of  an  emulsion  of  the  glands  into  a 
monkey  produced  the  disease  after  an  incubation  period  of  ten 
days.  In  no  other  instance  has  the  presence  of  the  virus  anywhere 
in  the  human  body  been  proved  except  in  the  central  nervous 
system.  Experiments  in  this  direction  have  been  so  far  few,  and 
more  extended  researches  are  necessary.  Similar  experiments  with 
monkeys  are  useful  as  supplementary  studies. 

(b)  In  Monkeys. — In  these  animals  the  central  nervous  system 
is  the  chief  place  where  the  virus  is  found,  more  particularly  in  the 
regions  corresponding  to  the  paralysed  limbs.  In  order  to  make 
as  sure  as  possible  of  a  successful  result,   those   segments   of  the 


g6  epidemic  infantile  paralysis 

cord  should  be  used  which  correspond  to  the  limb  most  recently 
attacked.  The  virus  is  found  wherever  the  typical  lesions  occur, 
i.e.,  in  the  medulla,  pons  and  brain. 

The  experience  of  most  authors  with  cerebrospinal  fluid  has 
been  negative  (Landsteiner  and  Levaditi,  Leiner  and  v.  Wiesner, 
Romer),  even  with  the  most  varied  methods  of  inoculation.  Flexner 
and  Lewis  alone  obtained  positive  results  and  only  when  they  used 
the  fluid  of  monkeys  which  had  received  either  intracerebral  or 
intraspinal  injections  of  the  virus  and  when  the  fluid  was  removed 
during"  the  pre-paralytic  stage.  They  found  also  that  the  fluid 
withdrawn  at  this  time  gave  evidence  of  a  recent  pial  infection, 
being  cloudy  and  containing  more  cells  than  normal  and  an  in- 
creased amount  of  albumin.  Human  cerebrospinal  fluid  presented 
the  same  appearances  and  Flexner  and  Lewis  express  the  hope  that 
with  the  aid  of  monkeys  the  inoculation  of  cerebrospinal  fluid  may 
prove  of  use  in  the  establishing  of  an  early  diagnosis.  At  the  same 
time  it  must  be  remembered  that  the  virus  has  been  found  only  in 
monkeys  infected  by  the  intracerebral  or  intraspinal  method,  which 
certainly  does  not  correspond  to  the  method  of  infection  occurring 
in  man.  Flexner  and  Lewis  report  that  when  paralysis  has  set  in 
the  cerebrospinal  fluid  becomes  clear  again,  as  is  the  case  in  man, 
and  that  it  no  longer  contains  virus  in  a  virulent  state. 

We  ourselves  have  been  unable  to  find  any  evidence  that  the 
virus  is  present  in  the  blood  of  infected  monkeys;  Flexner  and 
Lewis,  as  well  as  Leiner  and  v.  Wiesner,  have  had  the  same 
experience  in  the  main.  In  one  instance  the  Austrian  observers 
were  able  to  find  virus  in  the  blood;  this  was  during  the  paralytic 
stage.  They  have  never  found  it  in  the  stage  of  incubation,  which 
is  important  from  the  point  of  view  of  the  theory  that  the  virus 
is  carried  by  the  blood.  Flexner  and  Lewis  obtained  a  positive 
result  in  one  case  by  using  a  very  large  quantity  of  blood  (25  c.c. 
intravenously),  withdrawn  after  paralysis  had  set  in;  the  monkey 
became  ill  only  on  the  seventeenth  day,  so  that  the  amount  of  virus 
present  in  this  very  large  amount  of  blood  was  probably  small. 

Experiments  with  spleen  pulp,  liver,  kidney,  and  bone  marrow 
were  negative  throughout  and  confirmed  the  previous  negative 
results  with  blood  (Flexner  and  Lewis,  Leiner  and  v.  Wiesner).  In 
view  of  these  results  it  is  improbable  that  the  virus  is  carried  to 
any  extent  by  the  blood-stream. 

The  question  of  the  excretion  of  the  virus  has  been  studied  in 
a  number  of  experiments.  Saliva,  bile,  urine,  and  intestinal  con- 
tents have  been  found  free  of  virus  by  many  authors.  We  our- 
selves obtained  a  negative  result  when  using  the  contents  of  the 
small  intestine  of  a  monkey  which  had  severe  gastro-intestinal 
symptoms  and  in  which  the  mesenteric  glands  were  much  swollen 
and  contained  highly  virulent  virus. 

Monkey  50  (Rhesus). — On  April  25,  1910,  -received  simultaneously 
an  intracerebral  (1  c.c.)  and  an  intraperitoneal  (5  c.c.)  injection  of  extract 
of  the  contents  of  the  small  intestine  filtered  through  a  Berkefeld  filter  and 
remained  well. 


PATHOLOGY    AND    PATHOGENESIS  97 

At  first  we  considered  the  possibility  that  the  virus  was  excreted 
into  the  intestine,  but  in  view  of  the  experience  of  ourselves  and 
others  that  possibility  must  be  rejected;  even  the  injection  of  the 
mucous  membrane  of  the  stomach  and  intestines  has  produced  no 
result  (Flexner  and  Lewis,  Leiner  and  v.  Wiesner).  Landsteiner 
and  Levaditi  found  virus  once  in  the  saliva,  but  they  lay  little 
stress  on  this  case  in  view  of  the  consistently  negative  results  of 
their  further  experiments.  Leiner  and  v.  Wiesner  found  no  virus 
in  the  salivary  glands,   which  coincides  with  our  own  experience. 

So  far  the  injection  of  the  organs  of  monkeys  had  produced 
practically  no  results.  The  following-  positive  experiments  are  of 
more  importance.  Flexner  and  Lewis  began  with  the  idea  that, 
considered  epidemiologically,  there  were  many  points  of  similarity 
between  epidemic  poliomyelitis  and  epidemic  meningitis  (cf.  Chap- 
ter V).  In  previous  experiments  they  had  proved  that  in  monkeys 
previously  infected  intracerebrally  with  the  meningococcus  the 
organism  was  found  in  the  nasal  mucous  membrane;  conversely 
they  had  found  that  after  infection  of  the  nasal  passages  the  virus 
wandered  to  the  meninges.  It  now  occurred  to  them  to  examine 
whether  also  in  poliomyelitis  the  nasal  mucous  membrane  acts  as 
the  point  of  entrance  and  of  excretion  of  the  virus.  They  succeeded 
in  demonstrating  that  the  mucous  membrane  of  the  nose  and 
pharynx  of  monkeys  after  intracerebral  infection  contained  the 
virus;  emulsions  of  the  mucous  membrane,  filtered  through  a 
B'erkefeld  filter,  when  injected  into  the  brain  of  a  monkey,  promptly 
produced  paralysis.  The  blood  contained  in  the  mucous  membrane 
could  not  have  contained  the  virus  since  the  experiments  detailed 
above  had  proved  that  the  blood  contains  either  no  virus  or  at 
most  the  minutest  quantity.  Leiner  and  v.  Wiesner  confirmed  the 
results  obtained  by  the  American  experimenters.  Osgood  and 
Lucas  found  virus  in  the  mucous  membrane  of  the  nose  and 
pharynx  eight  wreeks  and  even  six  months  after  intracerebral 
infection.  Owing  to  the  remarkable  similarity  betwen  epidemic 
meningitis  and  poliomyelitis  one  is  inclined  to  believe  that  the  virus 
is  excreted  by  way  of  the  nasal  mucous  membrane,  but  the  fact 
must  not  be  lost  sight  of  that  there  is  no  direct  proof  available 
that  the  secretion  contains  the  virus;  Flexner  and  Lewis,  as  well 
as  myself,  have  failed  to  find  the  virus  in  mucus  from  the  nose  of 
human  beings. 

The  discovery  of  the  virus  in  the  olfactory  lobes  after  successful 
inoculation  of  the  nasal  mucous  membrane  by  Landsteiner  and 
Levaditi  is  of  first-rate  importance,  as  showing  that  the  virus  follows 
the  track  of  the  nerves. 

Experiments  showing  the  relation  of  the  glands  to  the  virus 
are  of  much  importance.  Flexner  and  Lewis  obtained  a  positive 
result  by  the  subcutaneous  method;  they  found  the  site  of  inocu- 
lation free  of  virus,  but  the  corresponding  glands,  as  well  as  the 
spinal  cord,  contained  virus.  The  virus  had  been  absorbed  by  way 
of  the  lymphatics  beyond  the  possibility  of  doubt.     Still  more  im- 

7 


98  EPIDEMIC  INFANTILE  PARALYSIS 

portant,  it  seems  to  me,  are  the  results  obtained  by  Joseph  and 
myself.  We  proved  that  after  intracerebral  injection  the  virus 
passed  to  the  mesenteric  glands. 

Monkey  38  received  an  intracerebral  injection  on  March  2,  1910. 
On  the  10th  depressed;  much  diarrhoea.  On  the  nth,  condition  the  same; 
in  addition,  slight  paresis  of  all  limbs;  12th,  universal  paralysis;  died  at 
noon.  The  autopsy  revealed  typical  microscopical  changes.  Swelling  of 
the  mesentric  glands  was  very  marked;  the  coils  of  intestine  appeared  red, 
and  the  lymph  follicles  and  Peyer's  patches  were  swollen.  The  mesenteric 
glands  were  proved  to  contain  no  bacteria  on  microscopical  examination, 
and  were  preserved  in  glycerine.  On  March  22,  monkey  42  received  an 
intracerebral  injection  of  an  emulsion  of  the  glands.  It  remained  well  until 
April  1.  On  the  2nd,  sudden  severe  paralysis  of  the  hind  limbs  and  slight 
paresis  of  the  fore  limbs  set  in  ;  the  paralysis  became  worse  during  the  day, 
and  was  total  in  all  limbs  by  the  evening.  The  animal  was  found  dead  on 
the  3rd.      The  autopsy  showed  typical,  intense  changes. 

I  shall  discuss  the  clinical  and  pathological  importance  of  this 
case  later.  Flexner  and  Lewis  obtained  an  opposite  result  even 
when  the  virus  was  injected  directly  into  the  alimentary  tract.  On 
the  other  hand,  the  more  systematic  research  of  Leiner  and  v. 
Wiesner  confirmed  and  amplified  our  results.  In  the  case  of 
monkeys  killed  during  the  first  days  of  illness  after  intracerebral 
injections  they  found  virus  in  the  submaxillary  glands,  glands  of 
the  neck,  the  mesenteric  and  prevertebral  glands ;  the  inguinal 
glands  were  found  to  be  free  of  virus.  In  so  far  as  these  experi- 
ments allow  of  a  general  interpretation  we  may  say,  that  after 
intracerebral  injection  in  monkeys  the  virus  passes  with  ease  from 
the  spinal  cord  to  the  glands  in  its  vicinity.  Leiner  and  v.  Wiesner 
arrived  at  the  conclusion  that  the  type  of  disease  produced  by 
inoculation  with  virus  from  the  glands  was  a  not  very  severe  one. 

Conclusions. — The  general  impression  produced  by  the  fore- 
going recital  of  results  obtained  is  perhaps  rather  confusing;  yet, 
on  the  whole,  the  results  make  up  a  very  uniform  picture  of  the 
distribution  of  the  virus  within  the  bodies  of  human  beings  and 
monkeys.  The  virus  has  a  strong  affinity  to  the  central  nervous 
system  and  is  found  in  the  greatest  quantity  there.  The  other 
organs  are  practically  free  of  the  virus.  The  relation  of  the  virus 
to  the  lymphatic  system  is  exceedingly  remarkable ;  it  seems  to 
indicate  that  the  virus  tends  to  spread  to  organs  which  contain 
much  lymphoid  tissue.  The  objection,  that  the  experiment  merely 
indicates  the  absorption  of  the  virus  from  the  alimentary  tract,  may 
be  brought  against  the  results  of  examination  of  the  mesenteric 
glands  in  man;  the  same  examination  in  monkeys,  which  had 
received  an  intracerebral  injection,  is  not  open  to  that  objection, 
and  the  result  shows  that  the  virus  travels  by  way  of  the  lymphatics 
and  possibly  develops  in  them.  At  first  I  was  inclined  to  look  upon 
the  presence  of  the  virus  in  the  mesenteric  glands  of  monkeys  which 
had  received  an  intracerebral  injection  as  evidence  that  the  virus 
was  carried  by  the  blood.    On  considering  the  results  as  a  whole  and 


PATHOLOGY    AND    PATHOGENESIS  99 

particularly  the  fact  that  the  blood  is  usually  free  from  virus,  it 
seems  to  me  more  probable  that  the  virus  passes  by  the  lymphatics. 
That  virus  has  been  found  in  the  mucous  membrane  of  the  nose 
and  throat,  is  a  further  instance  of  the  affinity  of  the  virus  for 
lymphatic  tissue;  Flexner  and  Lewis  hold  the  view  that  the  virus 
is  most  probably  carried  from  the  meninges  to  the  mucous  mem- 
brane by  the  lymph  channels.  Key  and  Retzius  proved  the  exist- 
ence of  such  channels  when  they  found  that  injection  of  the  sub- 
arachnoid space  caused  injection  of  the  lymphatics  of  the  nasal 
mucous  membrane.  The  marked  richness  in  lymphatic  tissue  of  the 
nose  and  throat  is  another  argument  in  favour  of  the  existence  of 
such  an  affinity. 

The  Methods  of  Inoculation. — From  all  that  we  know  of  the 
relation  the  virus  bears  to  the  central  nervous  system,  it  is  clear 
that  the  intracerebral  method  is  the  most  certain.  Intraspinal 
inoculation  is  usually  successful.  Leiner  and  v.  Wiesner  observed 
a  certain  regularity  in  the  occurrence  of  paralysis  after  intracerebral 
injection;  they  found  that  the  limb  opposite  to  the  side  where  the 
injection  was  made  was  affected  first  and  that  it  was  usually  the 
hind  limb.  They  made  the  injection  usually  into  the  central  con- 
volutions as  near  the  vertex  as  possible.  After  hearing  of  this 
observation  made  by  the  Austrian  writers,  we  re-examined  our 
material  from  this  point  of  view,  and  with  the  following  interesting 
result.  I  must  mention  first  that,  owing  to  the  position  of  the 
operating  table,  we  happened  to  make  all  our  injections  on  the 
left  side  of  the  skull  in  the  region  of  the  central  gyri;  in  the  case 
of  all  the  injections  we  entered  only  so  far  from  the  mid-line  as 
to  avoid  wounding  the  longitudinal  sinus.  This  situation  cor- 
responds with  the  fact  that  the  lower  limbs  were  affected  first  in 
most  of  our  cases.  Paralysis  appeared  first  in  the  left  hind  limb 
of  only  one  monkey  out  of  twenty  which  had  been  injected  on  the 
left  side.  In  eight  cases  one  side  was  not  affected  before  the 
other,  but  it  must  be  remembered  that  at  the  time  we  were  not 
paying  special  attention  to  this  point.  In  no  less  than  eleven 
experiments  the  limbs  on  the  right  side  were  paralysed  first.  In 
the  majority  of  the  cases  the  paralysis  began  in  the  right  hind  limb 
and  then  affected  the  left  hind  limb.  When  the  fore  limbs  were 
involved  first,  it  was  the  right  one,  with  one  exception,  which  was 
affected.  Unfortunately,  at  the  time  wThen  we  became  aware  of 
the  importance  of  this  question  we  had  almost  finished  our  series 
of  experiments.  I  may  mention,  however,  that  both  monkeys 
injected  ad  hoc  on  the  right  side  became  paralysed  first  in  the 
contralateral  limbs.  Should  these  observations  be  confirmed  they 
would  seem  to  indicate  that  the  active  agent  spreads  along  the 
neuron  or,  at  least,  spreads  more  quickly  in  this  direction  than  in 
any  other.  It  is  to  be  supposed  that  in  doing  this  it  passes  along 
the  lymph  channels  accompanying  the  neuron,  although  this  would 
pre-suppose  a  considerable  degree  of  isolation  of  these  channels. 
A  large   number   of   experiments,    directed   towards   this   particular 


IOO  EPIDEMIC   INFANTILE   PARALYSIS 

question,  are  necessary;  they  should  include  as  many  variations 
in  the  method  of  injection  as  possible. 

Direct  injection  into  the  nerves  is  a  method  which  is  of 
particular  interest.  The  authors  who  have  tried  this  method  are 
unanimous  that  it  is  very  effective  and  that  paralysis  always  occurs 
first  in  the  limb  corresponding-  to  the  nerve  injected  (Flexner  and 
Lewis,  Landsteiner  and  Levaditi,  Leiner  and  v.  Wiesner).  This  is 
confirmatory  of  the  views  expressed  by  Wickman,  Harbitz,  and 
Scheel,  that  the  virus  follows  the  course  of  the  nerves.  Leiner 
and  v.  Wiesner  designed  a  very  beautiful  experiment  to  illustrate 
the  point.  They  first  ligatured  the  sciatic  nerve  of  a  monkey,  then 
injected  the  nerve  peripheral  to  the  ligature  and  finally  severed  the 
nerve  at  the  ligature.  The  monkey  remained  well,  while  another 
monkey,  in  which  the  sciatic  nerve  was  injected  without  previous 
ligature,  quickly  became  paralysed  in  the  corresponding  limb.  This 
progress  of  the  virus  along  the  nerve  may  be  compared  with  the 
absorption  of  the  virus  of  rabies  and  of  tetanus.  If  we  accept  the 
view  of  Meyer  and  Ransom,  that  the  axis-cylinder  itself  carries 
the  virus  in  the  latter  case,  it  is  more  probable  that  the  living  virus 
of  poliomyelitis  wanders  in  a  centripetal  direction  along  the  peri- 
neural lymphatics.  The  experiment  confirms  Wickman's  theory 
that  the  virus  reaches  the  central  nervous  system  primarily  by  way 
of  the  nerves. 

Other  authors  incline  to  the  view  that  the  infection  is  hemato- 
genous. It  is  true  that  intravenous  injection  can  cause  the 
disease,  but  the  method  is  an  uncertain  one.  Landsteiner  and 
Levaditi  have  shown  that  successful  infection  is  produced  even 
when  the  virus  has  to  pass  through  the  liver  (injection  of  a  mesen- 
teric vein).  This  demonstration  that  infection  is  possible  via  the 
blood-stream  is  no  proof  that  the  virus  reaches  the  central  nervous 
system  by  that  channel.     We  shall  return  to  this  later. 

So  far  it  has  proved  impossible  to  inoculate  through  the 
unbroken  skin;  on  the  other  hand,  infection  by  subcutaneous  in- 
jection has  been  successful  in  a  few  instances.  The  virus  passes, 
in  part  at  least,  through  the  lymphatic  glands  (cf.  the  experiment 
of  Flexner  and  Lewis  quoted  above).  Direct  injection  into  the 
lymphatic  glands  has  been  successful.  As  in  rabies,  inoculation 
into  the  anterior  chamber  of  the  eye  has  produced  the  disease 
(Leiner  and  y.  Wiesner,  Landsteiner  and  Levaditi).  It  is  doubtful 
whether  intraperitoneal  injection  alone  will  give  a  positive  result. 

It  follows  from  all  these  successful  artificial  methods  of 
inoculation  that,  in  the  case  of  the  monkey,  which  is  as  susceptible 
as  man  to  the  disease,  a  positive  result  can  be  obtained  with 
certainty  only  when  the  virus  is  brought  into  direct  contact  with 
nervous  tissue.  These  experiments,  however,  only  go  to  prove 
what  route  the  virus  takes  when  it  is  once  within  the  body.  They 
show  that  the  active  agent  is  certainly  capable  of  reaching  the 
central  nervous  system  by  way  of  the  perineural  lymph  spaces. 
This  is  not  disproved  by  the  fact  that  direct  intravenous  injection 


PATHOLOGY    AND    PATHOGENESIS  IOI 

has  been  successful;  we  know  that,  in  the  case  of  tetanus,  intoxica- 
tion by  way  of  the  blood-stream  is  promptly  successful,  but  that 
the  toxin  does  not  pass  straight  from  the  blood  to  the  brain  and 
spinal  cord,  but  is  absorbed  by  the  peripheral  endings  of  the  nerves. 
It  is  interesting-  to  note  that  in  successful  intravenous  injections  the 
paralysis  occurred  first  in  the  upper  half  of  the  body,  i.e.,  in  the 
segments  of  the  cord  which  are  furnished  with  relatively  short 
peripheral  nerves. 

Attempts  to  determine  the  Point  of  Entrance  of  the  Virus.— 
The  following  experiments  help  to  elucidate  this  problem.  They 
are  based  upon  clinical  experience,  which  indicates  the  upper  and 
lower  respiratory  tract  (sore  throat,  coryza,  and  bronchitis)  or  the 
alimentary  tract  (gastro-intestinal  symptoms)  as  the  portal  by  which 
the  virus  enters.  It  is  not  easy  to  cause  infection  through  the 
nasal  mucous  membrane ;  Landsteiner  and  Levaditi  obtained  no 
results  through  the  undamaged  mucous  membrane ;  they  were 
successful  when  the  virus  was  injected  into  the  mucous  membrane, 
the  infection  following  the  nerves  (the  virus  was  found  in  the 
olfactory  lobe)  and  causing  the  "type  superieur  "  of  poliomyelitis. 
Flexner  and  Lewis  succeeded  by  rubbing  in  the  virus.  Leiner  and 
v.  Weisner  first  cocainized  the  mucous  membrane  and  then  rubbed 
in  the  virus  with  a  hard  brush.  Infection  through  the  nasal  mucous 
membrane  is  thus  undoubtedly  possible;  it  appears  to  be  necessary, 
however,  for  the  mucous  membrane  to  be  injured  in  some  way 
previously. 

Flexner  and  Lewis  had  no  success  with  tracheal  injections  and 
inhalation;  on  the  other  hand,  the  same  methods  proved  immediately 
successful  in  the  hands  of  Leiner  and  v.  Wiesner.  Paralysis 
occurred  in  these  cases  first  in  the  upper  half  of  the  body,  in  the 
neck  and  arms.  In  some  instances  the  paralysis  remained  limited 
to  these  regions,  in  others  it  descended.  The  same  authors  have 
done  much  to  clear  up  the  problem  of  infection  through  the 
alimentary  tract.  Their  experiments  had  no  result  at  first.  They 
then  fed  monkeys,  which  had  been  starved  for  twelve  to  twenty- 
four  hours,  and  in  which  peristalsis  had  been  diminished  by  means 
of  opium,  with  the  virus;  this  was  effective.  Paralysis  was  pro- 
duced also  by  direct  injection  of  virus  into  a  loop  of  small  intestine. 
In  these  experiments  the  paralysis  always  affected  the  lower  half 
of  the  body  first.  Krause  and  Meinicke  were  not  successful  by  the 
method  of  feeding  monkeys  with  virus,  nor  were  Landsteiner  and 
Levaditi,  although  they  used  large  quantities. 

One  is  impressed,  even  more  than  in  the  experiments  on  the 
nasal  mucous  membrane,  with  the  fact  that  infection  is  only  possible 
under  certain  conditions. 

These  experiments,  however,  give  some  support  to  the  clinical 
views  mentioned  above. 

Finally,  an  observation  may  be  recorded  here  which  has  been 
made  by  all  the  workers  in  this  field.  In  no  case  has  spontaneous 
infection  of  a  monkey  ever  been  observed.     In  the  course  of  our 


102  EPIDEMIC   INFANTILE   PARALYSIS 

own  experiments  healthy  monkeys  were  kept  in  quite  small  cages, 
together  with  monkeys  which  had  been  infected  and  with  those 
which  were  actually  suffering  from  the  disease.  Leiner  and  v. 
Wiesner  purposely  brought  healthy  monkeys  into  close  contact 
with  diseased  monkeys,  and  no  infection  resulted.  One  may 
suppose  that  monkeys  are  not  liable  to  infection  in  the  natural  way, 
although  this  is  contradictory  to  the  experience  that  they  can  be 
infected  by  way  of  the  natural  portals  of  entry  of  the  virus  and 
that  they  are  very  dirty  among  themselves.  It  is  more  probable 
that  the  artificially  infected  animals  do  not  excrete  the  virus.  It 
is  in  favour  of  this  theory  that  the  virus  was  never  transmitted 
to  anyone  who  was  occupied  with  the  animals,  nor  was  it  carried 
by  them  to  their  relatives  or  to  any  other  persons,  although  the 
animals  had  to  be  kept  in  our  laboratory  itself  from  lack  of  other 
rooms  which  could  be  kept   warm. 

III.— THE  PATHOLOGICAL  CHANGES  FOUND 
IN  EXPERIMENTAL  POLIOMYELITIS  IN 
MONKEYS  COMPARED  WITH  THOSE 
FOUND  IN  MAN. 

It  is  not  claimed  that  the  statements  made  in  this  section  are 
the  result  of  a  systematic  study  of  the  pathological  picture  presented 
by  experimental  poliomyelitis  in  monkeys,  and  they  should  not  be 
regarded  as  such.  Our  time  was  too  much  taken  up  with  the 
purely  experimental  side  of  the  work  (apart  from  other  studies 
altogether)  for  us  to  be  able  to  make  that  detailed  study  of  the 
histology  of  the  disease  which  is  both  necessary  and  desirable. 
We  were  obliged  to  use  a  great  deal  of  our  material  for  research 
into  the  nature  of  the  virus,  the  means  of  preserving  it  and  the 
question  of  immunity.  Usually  we  were  satisfied  with  the  examina- 
tion of  small  pieces  from  the  lumbar  cord,  particularly  the  lumbar 
enlargement,  the  cervical  enlargement,  the  medulla,  the  central 
ganglia  and  the  cerebral  cortex.  We  consider  such  an  examination 
to  be  of  the  utmost  importance,  even  though  the  clinical  symptoms 
appear  quite  conclusive;  otherwise  serious  errors  may  occur,  as  in 
our  experience  with  cerebral  abscesses.  Histological  examination 
is  very  reliable ;  in  cases  where  we  saw  no  lesions  we  were  unable 
to  prove  the  presence  of  virus.  On  the  other  hand,  the  finding 
of  typical  acute  microscopical  changes  was  followed  usually  by  a 
positive  result  in  the  inoculation  experiment.  I  will  say  at  once 
that  we  made  no  microscopical  examination  of  organs,  apart  from 
the  central  nervous  system.  As  far  as  I  know  there  is  only  one 
observation  on  record :  Plexner  found  a  round-celled  infiltration 
close  to  a  vessel  at  the  site  of  a  subcutaneous  inoculation.  There 
is  a  wide  field  for  research  in  this  direction.  The  lymphatic  glands 
might  repay  study;  they  are  known  to  contain  the  virus,  and  I 
think  therefore  that  a  specific  lesion  may  be  found" in  them. 


PATHOLOGY    AND    PATHOGENESIS  103 

Technique Directly    after    the     death,     or    after    the    killing    of    the 

dying  monkey,  the  portions  of  the  nervous  system  mentioned  above  were 
cut  out  and  put  into  7  to  S  per  cent,  formalin  for  twenty-four  hours  or  longer. 
They  were  then  hardened  in  alcohol  of  increasing  strength  for  at  least 
three  days.  iVfter  being  completely  dehydrated  in  absolute  alcohol  they 
were  transferred  to  xylol,  where  they  remained  until  they  were  quite  clear,, 
usually  two  to  three  hours ;  the  xylol  was  changed  twice.  Then  they  were 
put  into  a  concentrated  solution  of  pure  xylol  and  soft  paraffin  for  two  to. 
three  hours,  then  into  paraffin  with  a  melting  point  of  420  for  one  hour,, 
for  five  hours  into  paraffin  with  a  melting  point  of  4S0,  and,  finally,  they 
were  embedded. 

The  sections,  about  15  n  thick,  were  cut  with  a  microtome,  and  stained 
either  with  hsematoxylin  and  eosin  or  with  van  Gieson.  For  demonstrating 
any  bodies  which  might  be  included  in  the  cells  we  used  Joest's  modification 
of  Mann's  stain,  which  he  used  for  Negri  bodies;  as  I  have  mentioned 
above,  we  found  no  such  bodies. 

Thus  I  am  unable  to  give  results  of  a  systematic  nature.  This, 
necessary  limitation  perhaps  does  not  involve  any  great  loss;  after 
examining  the  brain  and  spinal  cord  for  diagnostic  purposes  in 
about  forty  monkeys,  I  am  sure  that  a  full  description  of  them 
would  be  monotonous.  I  shall  confine  myself  to  a  summary 
description,  with  the  aid  of  micro-photographs,  of  the  changes 
found,  and  I  shall  compare  these  with  the  appearances  in  human 
poliomyelitis  described  by  Wickman. 

Macroscopic  Changes. — In  monkeys  which  have  died  of  acute 
poliomyelitis  no  changes  are  found  outside  the  central  nervous 
system  in  most  cases.  Occasionally  small  areas  of  broncho- 
pneumonia were  present,  usually  only  in  those  monkeys  in  which 
the  death  agony  was  prolonged.  These  changes  can  hardly  be  due 
to  the  action  of  the  virus.  Redness  of  the  intestinal  mucous  mem- 
brane was  common,  but  is  probably  of  but  little  significance  owing* 
to  the  frequency  of  intestinal  disturbance  in  monkeys  kept  in 
captivity.  On  the  other  hand,  we  are  inclined  to  attach  importance 
to  the  swelling"  of  the  lymph  follicles  and  of  Peyer's  patches,  and 
particularly  to  the  enlargement  of  the  mesenteric  glands,  since  they 
have  been  shown  to  contain  virus.  Landsteiner  has  observed  in- 
flammatory swelling's  in  the  neck,  which  were  more  marked  than 
those  due  to  the  pharyngitis  which  is  so  common  in  these  animals. 
Other  pathological  appearances  have  not  been  seen  in  monkeys. 

In  human  beings  the  spleen  is  swollen  sometimes;  cloudy 
swelling  and  even  inflammation  of  the  kidneys  has  been  observed, 
and  in  some  cases  the  tonsils  were  sw'ollen  (Beneke).  Swelling" 
of  the  follicles  and  Peyer's  patches  were  relatively  common. 

The  macroscopic  changes  in  the  brain  and  spinal  cord  of  mon- 
keys dead  from  acute  poliomyelitis  may  be  so  little  characteristic, 
that  even  when  one  has  had  much  experience  it  is  not  possible  to 
say  definitely  whether  a  lesion  is  present  or  not,  and  certainly  not 
to  say  that  true  poliomyelitis  is  present,  even  when  the  microscope 
reveals  typical  and  well-marked  changes.  In  the  majority  of  cases, 
however,  macroscopic  changes  are  more  obvious.     On  removal  of 


io4 


EPIDEMIC   INFANTILE   PARALYSIS 


the  skull-cap  the  pressure  within  the  dura  is  found  to  be  raised; 
there  is  an  excessive  flow  of  clear  cerebrospinal  fluid  when  the 
dura  is  turned  down.  The  pia  mater  on  the  surface  of  the  brain 
is  congested,  the  surface  itself  is  shiny  and  moist.  Compared  with 
the  normal  monkey's  brain,  which  is  of  a  yellowish  white  colour, 
the  brain  appears  diffusely  red;  on  section  this  redness  is  seen  to 
be  most  marked  in  the  grey  matter,  which  has  an  almost  violet 
tinge.     The  convolutions  are  often  flattened.     On  section  the  brain 


"  S  '   "  ,     -*■*  v-.-'c  '. 

h,:-  \*s$  -TV^y '■  .  '•-'  *  '.  '--A  .  -  i-- 


v.-  -•*--^.-K 


Fig.  17. 

The  greater  part  of  the  right  half  of  the  spinal  cord  of  a  normal  monkey. 
Above  and  to  the  left,  the  anterior  longitudinal  fissure ;  above  the  centre, 
the  right  anterior  horn.      To  the  left,  and  below,  the  posterior  horn. 


is  markedly  cedematous.  The  changes  in  the  spinal  cord  are  more 
■constant.  The  dura  is  more  distended  than  usual,  and  an  excessive 
amount  of  fluid  escapes  when  it  is  opened.  In  quite  acute  cases 
only  is  there  a  slight  opacity,  with  a  corresponding  increase  in  the 
•number  of  cells  present  (lymphocytes).     Generally  it  is  quite  clear. 


PATHOLOGY    AND    PATHOGENESIS 


I05 


The  pia  mater  is  congested.  The  cord  is  moist,  smooth,  and  in 
places  softer  than  normal,  although  without  any  true  softening 
being  present.  The  grey  matter  is  distinctly  more  red  than  normal; 
this  is  most  marked  in  the  segments  corresponding  to  the  distribu- 
tion of  the  paralysis.  The  anterior  horns  are  most  affected,  but 
frequently  the  whole  grey  matter  stands  out  in  a  red-violet  colour. 
On  looking  closely  minute  drops  of  blood  are  seen  in  the  grey 
matter;    microscopical    examination    shows    that    these    are    almost 


■S-^^l 


n& 


■  "■'•  •>■/  - 


Fig.  18. 

Section  of  the  lumbar  cord  of  monkey  Xo.  58.  To  the  right  and  above, 
the  slightly  affected  right  anterior  horn  with  infiltration  into  its  substance  and 
into  the  veins.  In  the  middle,  the  central  canal;  just  to  the  left  an  in- 
filtrated artery;  still  more  to  the  left,  the  left  anterior  horn,  slightly 
infiltrated. 


always   haemorrhages   into   the   substance   of  the   cord.     The  white 
matter  appears  quite  normal  or  perhaps  slightly  cedematous. 

The  macroscopical  appearances  in  man  are  so  exactly  similar 
to  those  just  described  that  it  is  unnecessary  to   deal   with  them. 


io6 


EPIDEMIC   INFANTILE   PARALYSIS 


Definite  morbid  changes  appear  to  be  rather  less  frequent;  that 
they  are  relatively  more  marked  in  the  monkey  may  be  due  to  the 
intracerebral  method  of  infection. 

Microscopic  Changes. — In  monkeys  these  are  usually  much 
more  widespread  than  would  be  expected  from  the  macroscopic 
changes  or  the  clinical  symptoms.  The  microscopic  lesions  are- 
more  intense  and  constant  in  the  spinal  cord  than  in  the  brain.  I 
mention  this  point  specially  because  we  are  dealing  with  monkeys 
infected  by  way  of  the  brain.  In  most  cases  a  glance  at  the  section 
under  a  low  magnification  is  enough  to  settle  the  diagnosis.  The 
most  obvious  change  seen  is  the  remarkable  increase  in  the  number 


Fig.  19. 

Shows  marked  changes  in  the  left  anterior  horn  and  part  of  the  posterior 
horn  of  the  lumbar  cord  of  monkey  No.  24. 

of  cell  nuclei;  this  is  most  marked  in  the  anterior  horns.  In  fig.  17* 
I  reproduce  the  appearances  of  the  normal  spinal  cord;  figs.  18,  19, 
and  20  represent  sections  showing'  the  changes  due  to  poliomyelitis 
under  the  same  magnification.     The  difference  is  clear  even  in  the 


*  The  photographs,  figs.  17  to  49,  were  taken  by  myself  by  means  of  a 
Zeiss  microphotographic  apparatus  kindly  lent  to  me  by  the  firm  of  Behring 
in  Marburg.  The  objectives  AA,  D  and  E  were  used,  and  in  order  to  obtain 
different  enlargements  the  length  of  the  tube  was  varied,  and  not  the  eye- 
piece. Unfortuntely,  I  omitted  to  note  how  far  the  tube  was  drawn  out  in 
each  case,   so  that  I  am  unable  to  give  the  exact  amount  of  enlargement. 

Most  of  the  photographs  were  taken  with  objective  AA  and  a  tube  of 
'65  m. 


PATHOLOGY    AND    PATHOGENESIS 


107" 


case  of  monkey  No.  58  (for  the  clinical  history  see  p.  77),  in  which 
the  changes  are  only  slight;  it  is  very  obvious  in  figs.  19  and  20, 
taken  from  the  severely  affected  spinal  cords  of  monkeys  Nos.  24- 
and  4  (cf.  p.  66  and  p.  42),  which  print  more  darkly,  owing  to  the 
increased  number  of  cell  nuclei.  These  illustrations,  taken  with  a 
low   power,    show   that  the   posterior   horns   are   also   affected.     A 


Fig.  20. 

Anterior  and  posterior  horns  from  the  lumbar  region  of  monkey  No.  4 ; 
well-marked  changes.  The  dark  areas  in  the  left  anterior  horn  are  mainly 
haemorrhages.  To  the  right  above,  a  pial  septum  infiltrated.  At  the  right 
border,  the  fold  of  the  pia  lying  in  the  anterior  longitudinal  fissure,  much 
infiltrated.  Below,  veins  with  marked  infiltration,  some  of  them  passing 
to  the  posterior  horn. 


higher  magnification  is  necessary  in  order  to  analyse  the  nature  of 
the  lesions. 

Pia. — In  the  lower  part  of  the  cord  the  pia  is  much  affected. 
I  found  that  involvement  of  the  pia  was  most  marked  in  the  lower 
lumbar    region,    and    became    less    in    an    upward    and    downward 


ioS 


EPIDEMIC   INFANTILE   PARALYSIS 


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<■■  ■'"'  '7/  '  '/•■'<%'*i:'~£'-':'', 

ii 

'WW 

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Fig. 

21. 

Slight   infiltration   of   the  pia   at   the   entrance   to   the   anterior   longitudinal 
fissure  in  monkey  Xo.   2.     Also  some  infiltration  within  the  fissure. 


Fig.  22. 

Well-marked  round  cell  infiltration  in  the  deeper  part  of  the  anterior  fissure 
(from  the  lumbar  cord  of  monkey  Xo.  2). 


PATHOLOGY    AND    PATHOGENESIS  109 

direction  from  that  region.  Irregularly  scattered  changes  in  the  pia 
are  found  in  the  upper  segments  of  the  cord  in  varying  degrees. 

The  chief  change  in  the  pia  is  a  round  cell  infiltration,  which  is 
partly  diffuse  and  partly  in  connection  with  the  vessel  walls. 

This  infiltration  is  more  marked  on  the  anterior  surface  of 
the  cord,  but  is  found  also  on  the  posterior  surface.  A  few  round 
cells  are  found  in  the  posterior  septum,  but  both  at  the  entrance 
to  the  anterior  fissure  and  in  the  deeper  parts  of  the  process  of  pia 
mater  the  infiltration  is  frequently  considerable  in  amount. 

Fig.  22  gives  some  idea  of  the  amount  of  infiltration.  Some- 
times infiltration  occurs  on  the  antero-lateral  aspect  of  the  cord; 
I  found  such  a  condition  in  a  monkey  which  had  been  ill  for  only- 
twelve  to  twenty-four  hours  (fig.   23). 


Fig.  23. 

Marked  round  cell  infiltration  of  the  pia  on  the  right  anterior  aspect  of  the- 
lower  lumbar  cord  of  monkey  Xo.   1. 

Infiltration  of  the  pia  is  often  seen  between  the  nerve  bundles 
of  the  anterior  or  posterior  roots.  The  blood-vessels  in  the  pia 
are  usually  distended  and  full  of  well-preserved  corpuscles.  Peri- 
vascular infiltration  is  most  marked  in  the  depths  of  the  anterior 
fissure;  the  infiltrated  vessels  can  be  seen  curving  outwards  to  reach 
the  anterior  horns.  More  rarely  a  pial  septum  passing  through  the 
white  matter  is  seen;  I  have  never  observed  any  direct  extension 
of  the  infiltration  from  the  pia  to  the  white  matter. 

The  pia  mater  of  the  brain  shows  similar  changes,  not  only  at 
the  site  of  inoculation,  where  they  are  invariable,  but  also  on  the 
base  of  the  brain  (vide  fig.  24). 

I  found  the  dura  mater  normal  in  every  case. 


i  IO 


EPIDEMIC   INFANTILE   PARALYSIS 


FIG.    24. 

Infiltrated  pia  from  the  base  of  the  brain  of  monkey  Xo.  4  at  the  entrance 
-to  a  sulcus.     Above  and  to  the  right  there  is  a  septum  slightly  infiltrated, 
passing  into  the  cortex.     The  infiltration  is  shown  surrounding  a  distended 
-vessel. 


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m«      ■    '        *    '  <  ■ 

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Fig.  2^ 


General  view  of  a  longitudinal  section  of  a  human  spinal  cord  from  a 
.case  of  poliomyelitis.  In  the  middle,  the  pia  with  much  infiltration  around 
-the  vessels;  to  the  right  and  left  of  the  pia,  normal  white  matter;  still  further 

outwards  on  both  sides,  the  markedly  infiltrated  anterior  horns.     On  the  left 

side  more  white  matter  is  seen. 


PATHOLOGY    AND    PATHOGENESIS 


III 


The  condition  of  the  pia  is  sufficient  to  explain  the  irritative 
symptoms  observed  in  some  monkeys  (hyperesthesia  and  vomiting"). 

The  pathological  changes  found  in  the  pia  in  human  beings 
correspond  very  closely  with  those  just  described.  The  pia  mater 
of  the  brain  appears  to  be  affected  more  frequently  and  more 
markedly  in  monkeys  than  in  man;  the  reasons  for  this  are  probably 
those  given  above. 

Spinal  Cord. — In  the  spinal  cord  itself  the  grey  matter  is 
undoubtedly  the  part  mainly  affected.  This  is  very  clearly  demon- 
strated by  means  of  longitudinal  sections.  Professor  Beneke  has 
very  kindly  allowed  me  to  make  use  of  one  of  his  own  longitudinal 
sections  of  the  spinal  cord  from  a  case  of  poliomyelitis  from  which 
I  have  made  photographs. 


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i  ■  ...  •"■■■  .hV'}!:v^^^:V7 

,  ■•>.   ..  •-    v  •;.  *:"■<■•  *-\*: M^ 


Fig.  26. 

Portion  of  a  longitudinal  section  of  the  same  spinal  cord  as  in  fig.  25. 
From  left  to  right,  a  portion  of  the  left  anterior  tract,  the  fold  of  pia  mater 
with  marked  infiltration,  the  right  anterior  tract,  the  right  anterior  horn 
invaded  by  round  cells. 


The  general  view  (fig.  25)  shows  the  two  infiltrated  anterior 
horns  lying  between  bundles  of  normal  white  matter.  The  median 
fissure  contains  infiltrated  pia  mater.  The  condition  is  seen  more 
clearly  under  a  higher  power  (fig.  26). 

The  increase  in  the  number  of  nuclei  affects  the  anterior  horns 
most;  it  is  not  seen  all  over  the  anterior  horns,  but  stands  in  a 
definite  relationship  to  the  vessels.  Very  frequently  infiltrated 
vessels  are  seen  passing  from  the  edge  of  the  fold  of  pia  lying  in 
the  anterior  fissure  to  the  anterior  horns  and,  sometimes,  to  the 
posterior  horns  (vide  fig.  27).  The  peripheral  vessels  are  affected 
as  often  as  the  central  vessels  (vide  fig.  28).     The  infiltration  usually 


112 


EPIDEMIC  INFANTILE  PARALYSIS 


affects  the  adventitia,  more  rarely  the  perivascular  lymph  spaces.  I 
agree  with  Wickman  that  the  veins  are  more  frequently  involved. 

The  manner  in  which  the  infiltration  affects  the  vessels  more 
than  the  general  substance  of  the  cord  is  well  shown  in  fig.  29. 

In  fig.  30  a  slightly  infiltrated  artery  and  several  veins  with 
marked  infiltration  are  seen.  In  some  instances  the  diffuse  infiltra- 
tion does  not  seem  to  have  any  relation  to  the  distribution  of  the 
vessels  (figs.  31,  32),  although  it  is  very  difficult  to  be  sure  on  this 
point. 

Sometimes,  more  usually  in  the  anterolateral  portion  of  the 
anterior  horns,  small  infiltrations  are  seen  which  are  quite  uncon- 
nected with  any  vessel;  from  their  situation  I  judge  that  they  are 
determined  by  the  presence  of  the  ganglion  cells. 


Fig.  27. 
Lumbar  cord  of  monkey  No.  4. 
(cf.  fig;.  20).  Above,  the  deepest 
part  of  the  anterior  fissure  with 
its  pia.  In  the  middle  and  below, 
blood-vessels  passing  to  the  pos- 
terior horn,  much  infiltrated. 


FIG.    28. 

Lumbar  cord  of  monkey  No.  4. 
Antero-lateral  portion  of  left 
anterior  horn.  To  the  left,  some 
peripheral  vessels,  much  infil- 
trated, passing  from  the  white  into 
the  grey  matter.  The  collections 
of  cells  seen  to  the  right  are  not 
made  up  of  round  cells,  but  are 
haemorrhages.  Markedly  degene- 
rate ganglion  cells  are  seen  lying 
in  the  loose,  cedematous  tissues  of 
the  cord. 


The  involvement  of  the  vessels  is  shown  further  by  their 
engorgement,  which  is  more  noticeable  in  the  case  of  the  veins. 
When  stained  with  van  Gieson  the  vessels  are  seen  filled  with  well- 
preserved  blood  corpuscles.  Haemorrhages  into  the  cord  are  not 
rare  in  acute  cases;  they  are  associated  usually  with  interstitial 
inflammation  (cf.  fig.  20).  Finally,  the  oedema  remains  to  be  con- 
sidered,   which    sometimes    causes    considerable    loosening    of    the 


PATHOLOGY     AND     PATHOGENESIS 


I  I 


Fig.  29. 

Another  view  of  the  same  section  as  in  figs.  25  and  26.  In  the  right 
half  of  the  illustration,  two  peripheral  vessels  with  marked  infiltration,  lying 
at  the  boundarv  between  white  and  grey  matter.  Otherwise  similar  to 
fig.  26. 


Fig.  30. 

Lumbar  cord  of  monkey  No.  58  [cf.  fig.  18).  To  the  left,  the  central 
canal ;  close  to  it,  an  artery  with  slight  infiltration.  An  infiltrated  vein  is 
seen  running  to  the  anterior  horn  (upwards  and  to  the  right  in  the  photo- 
graph).    Some  diffuse  infiltration  in  the  anterior  horn  (to  the  right,  above). 


ii4 


EPIDEMIC   INFANTILE   PARALYSIS 


tissues.  This  I  found  most  frequently  in  the  region  of  Clarke's 
column  in  the  upper  lumbar  region  (cf.  fig.  33);  the  tissues  were 
distended  and   formed  a  wide  mesh-work.     It  cannot  be  merely  a 


Fig.  31. 

Left  anteiior  horn  in  the  lumbar  cord  of  monkey  No.  46.  The  apex 
of  the  horn  lies  above.  To  the  ri^ht,  a  vessel  slightly  infiltrated.  In  the 
middle  and  above  to  the  right,  diffuse  infiltration  of  the  grey  matter. 


FIG.    32. 

Right  anterior  horn  (apex  above)  in  the  lumbar  cord  of  monkey  No.  24. 
Marked,  diffuse  infiltration.  The  tissues  are  swollen  with  oedema.  Vessels 
slightly  infiltrated.     Ganglion  cells  have  almost  disappeared. 

matter   of   chance   that   Wickman   found   a    similar   condition   most 
marked  in  that  region  in  man  also. 


PATHOLOGY    AND    PATHOGENESIS  1 15 

Three  kinds  of  alteration  of  the  ganglion  cells  were  to  be  seen 
in  my  preparations.  In  many  instances  they  had  simply  disappeared, 
and  it  was  impossible  to  say  how  this  had  happened.  It  was  as 
though  they  had  dissolved  like  a  lump  of  sugar  in  water.  It  seems 
to  me  not  improbable  that  the  oedema  is  the  active  agent  in  this 
process.  In  other  cases  a  microscopical  change  preliminary  to 
disintegration  could  be  seen.  The  cells  lose  their  polygonal  shape, 
the  protoplasm  has  a  washed-out,  homogeneous  appearance,  the 
nucleus  stains  poorly.  After  making  due  allowance  for  the  possi- 
bility of  error  which  Wickman  has  pointed  out.  that  only  portions, 
of  normal  cells  are  seen  in  the  sections,  I  was  able  by  means  of 
serial  sections  to  convince  myself  that  this  variety  of  alteration 
exists.     Strauss  has  shown  that  the  first  change  which  takes  place 


Fig.  33- 

Upper  lumbar  region  in  monkey  No.  48.  Near  Clarke's  column.  The 
tissues  are  disintegrated.  A  small  haemorrhage  is  present  to  the  left  and 
somewhat  upwards. 

in  such  cases  is  a  swelling  of  the  intracellular  network  of  neuro- 
fibrils. Such  a  change  may  be  the  forerunner  of  the  alterations- 
described  above,  and  lead  ultimately  to  the  complete  disappearance 
of  the  cell.  The  third  method,  which  is  the  most  unequivocal,  is 
that  usually  called  neuronophagy.  It  seems  to  occur  more  fre- 
quently in  monkeys  than  in  human  beings.  In  his  earlier  researches- 
Wickman  met  with  it  so  rarely  that  he  did  not  consider  it  of  much 
pathological  importance.  In  monkeys  it  occurs  frequently,  and 
several  stages  can  be  made  out.  Figs.  34,  35  and  36  show  a  certain 
degree  of  neuronophagy  under  a  low,  moderate,  and  high  magnifi- 
cation; in  figs.  37,  38,  39  and  40  an  advanced  stage  of  neuronophagy 
is  seen. 


lib 


EPIDEMIC   INFANTILE   PARALYSIS 


The  illustrations  show  that  neuronophagy  consists  in  invasion 
of  the  ganglion  cells  by  round  cells;  the  latter  devour  the  former 
until  nothing  is  left  of  the  substance  of  the  ganglion  cells,  and  only 
swollen  round  cells  remain.  Wickman's  suggestion  is  correct,  that 
neuronophagy  occurs  frequently  in  acute  cases  of  poliomyelitis  in 
monkeys.  I  believe  that  it  is  just  because  poliomyelitis  is  so  acute 
in  monkeys,  as  compared  with  the  disease  in  man,  that  neurono- 
phagy is  so  often  seen  in  the  former.  The  following  clinical  histories 
show  that  the  examples  of  neuronophagy  recorded  above  were 
obtained  from  monkeys  in  which  the  disease  ran  a  particularly  acute 
course. 

Monkey  Xo.  35  suffered  for  a  considerable  time  from  the  disease,  but 
the  paralysis  which  caused  death  came  on  very  suddenly  in  the  form  of  a 
relapse. 


Fig.  34- 
Left  anterior  horn  from  the  lum- 
bar region  of  monkey  Xo.  35. 
Active  neuronophagy  beginning  in 
the  ganglion  cells.  Moderate  in- 
filtration  of  the  anterior  horn. 


FIG.    35- 
Enlargement    of    part    of  fig.   34. 
The    neuronophagy    is  more    easily 
seen. 


Monkey  Xo.  24  received  an  intracerebral  injection  of  the  virus  on 
January  25,  1910.  On  the  29th  it  became  suddenly  completely  paralysed, 
and  it  was  found  dead  on  the  following  morning. 

Marked  destruction  of  the  ganglion  cells  was  usually  accom- 
panied by  well-marked  interstitial  changes.  Where  this  appeared 
not  to  be  the  case  I  found  either  that  the  tissues  were  much  swrollen 
with  oedema,  or  that  the  vessels  in  the  neighbourhood  wrere 
markedly  infiltrated.  Even  when  there  was  no  connection  between 
infiltration  and  destruction  of  the  ganglion  cells,  in  almost  every 
case  infiltration  was  present  in  some  part  of  the  section.     In  order 


PATHOLOGY    AND    PATHOGENESIS 


117 


to  come  to  a  conclusion  on  this  point,  it  would  be  advisable  to  kill 
and  examine  monkeys  in  an  earlier  stage  of  the  disease — directly 
after  the  appearance  of  the  paralysis.  With  our  small  material  we 
were  unable  to  carry  out  this  plan.  In  selecting  areas  for  purposes 
of  photography.  I  tried  to  find  one  which  showed  this  destruction 
of  ganglion  cells  in  the  absence  of  infiltration  of  the  interstitial 
substance;  the  failure  which  attended  my  search  has  led  me  to 
believe  that  such  destruction  does   not   occur.     The  contrary  con- 


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Fig.  36. 

High   magnification  of  the   part    outlined    in    fig.    35.      Four  ganglion    cells 
undergoing  neuronophagy. 


dition  is  frequently  found;  cells  which  are  quite  normal,  as  far  as 
can  be  proved  microscopically,  are  seen  near  or  even  in  the  middle 
of  areas  of  infiltration. 

The  posterior  horns  are  usually  less  affected;  they  sometimes 
show  one  infiltrated  vessel  (fig.  41). 

In  confirmation  of  Wickman's  observation  in  human  beings, 
that  in  the  upper  lumbar  and  lower  dorsal   regions   the   posterior 


ii8 


EPIDEMIC   INFANTILE   PARALYSIS 


horns  seem  to  bear  the  brunt  of  the  attack,  I  may  refer  to  the  section 
made   from   the   upper  lumbar  region  of  monkey  No.   48;   fig.   42 


Fig.  37. 

lumbar  cord  of  monkey  No.  24.  Left  anterior  horn.  An  infiltrated 
septum  is  passing-  from  the  white  matter  above  and  to  the  left  to  the  anterior 
horja.     Marked  neuronophagy  in  the  horn. 


Fig.   38. 
Increased  magnification  of  the  part  outlined  in  fig.   37. 


represents  the  anterior  horn,  but  little  damaged;  fig.  33  the  marked 
swelling  up  of  the  tissues  in  the  region  of  Clarke's  column;  and 


PATHOLOGY    AND    PATHOGENESIS 


119 


Fig.  39- 
Still  higher  magnification  of  the  part  outlined  in  fig.  38. 


Fig.  40. 
Very  high  magnification  of  the  part  outlined  in  fig.  39. 


I.20  EPIDEMIC   INFANTILE  PARALYSIS 

fig.  43  the  changes  in  the  posterior  horn  in  the  same  section. 
Speaking-  generally,  however,  the  changes  are  much  less  marked  in 
the  posterior  horns,  and  the  nervous  tissue  suffers  much  less 
destruction  in  them. 

In  the  neighbourhood  of  the  central  canal,  tissue  infiltration  is 
generally  only  slight,  but  the  vessels  are  much  involved,  the  arteries 
relatively  less  than  the  veins  (fig.  30).  I  always  found  the  ependyma 
unaffected.  Wickman  occasionally  observed  infiltration  of  it  in 
human  beings. 

When  the  white  matter  is  affected  at  all,  it  shows  only  slight 
infiltration  of  the  tissues  or  of  the  vessels.  An  infiltrated  pial 
septum  may  traverse  the  white  matter,  but  the  infiltration  never 
invades    the    white    matter    itself.     I    could    not    find    any    relation 


Fig.   41. 
Infiltrated  vessel  in  the  right" posterior  horn:  from  the  middle  of  the  lumbar 

cord  of  monkey  No.  4. 

between  the  areas  affected  in  the  white  matter  and  those  in  the 
grey. 

I  did  not  examine  the  spinal  ganglia.  According  to  Flexner 
and  Lewis,  Landsteiner  and  Levaditi,  changes  are  seen  in  them 
similar  to  those  observed  in  man,  diffuse  infiltration  lying  between 
the  ganglion  cells  and  between  the  nerve  fibres  while  the  ganglion 
cells  are  degenerate. 

The  peripheral  nerves  were  not  examined.  Slight  degenera- 
tive changes  have  been  observed  in  human  beings,  but  no  inflam- 
matory lesions  (Redlich,  Monckeberg). 

Changes  similar  to  those  in  the  spinal  cord  are  found  in  the 
medulla  and  pons.  The  areas  affected  are  generally  smaller,  further 
apart   from   one   another,   and   distributed   in   an   irregular  manner. 


PATHOLOGY    AND    PATHOGENESIS 


121 


The  vessels  are  most  affected,  and  this  is  very  obvious  because  of 
the  distance  between  the  areas  involved.  Wickman's  observation 
that  these  areas  bore  no  relation  to  the  nuclei  of  the  cranial  nerves 


x£ 


\ 


Fig.   42. 

Anterior  horn,  slightly  infiltrated,  from  the  upper  part  of  the  lumbar  cord 

of  monkey  Xo.  4S. 


*:>■ 


Fig.    43. 


Round  cell  infiltration  in  the  posterior  horn  from  the  upper  lumbar  region 

of  monkey  Xo.  48. 


is  generally  true  also  in  monkeys.  Occasionally  very  distinct,  small 
infiltrations  are  seen  which  are  clearly  in  relation  to  ganglion  cells; 
they  are  found  to  be  examples  of  neuronophagy.       On  the  other 


122 


EPIDEMIC   INFANTILE   PARALYSIS 


hand,  infiltration  of  the  vessels  in  the  pons  and  medulla  is  common, 
even  when  the  clinical  history  does  not  lead  one  to  expect  it. 

Brain. — Infiltration  is  seen  most  frequently  (when  it  is  seen  at 
all)  in  the  cortex  near  the  site  of  inoculation.  It  is  often  not  more 
intense  than  that  found  elsewhere  in  the  brain,  i.e.,  in  the  opposite 
hemisphere,  at  the  base  of  the  brain,  and  in  the  central  ganglia. 
Figs.  44  and  45  represent  lesions  in  the  cortex  of  the  side  opposite 
to  the  injection  from  a  case  which  appeared,  clinically,  to  be  one 
of  cerebral  paralysis  (monkey  No.  27,  cf.  p.  53). 

The  outstanding  feature  is  the  great  degree  of  involvement  of 
the    vessels,    while    the    infiltration    of    the    tissues    is    only    slight. 


Fig.   44. 

Marked  infiltration  of  the  vessels  of  the  cerebral  cortex  of  monkey  No.   27, 
with  slight  general  infiltration. 


Fig.  47  shows  one  of  the  infiltrated  vessels  in  fig.  44  under  a  higher 
magnification. 

The  distribution  of  the  areas  is  very  irregular  in  the  brain,  as 
in  the  medulla.  They  are  far  apart  and  the  component  round  cells 
are  not  numerous  or  closely  massed  together  in  the  infiltrations  of 
the  tissues.  It  is  remarkable  that  in  many  cases,  where  inoculation 
was  performed  by  the  intracerebral  method,  no  trace  of  lesions  in 
the  brain  could  be  found. 

I  did  not  investigate  the  cerebellum.  In  man,  lesions  similar 
to  those  in  the  cerebrum  are  found.  Neither  was  I  able  to  give 
much  attention  to  the  character  of  the  cells  forming  the  infiltrations. 
As  far  as  I  can  judge,  Wickman's  interpretation  applies  equally  well 
to  the  appearances  found  in  monkeys.     It  is  well  known  that  there 


PATHOLOGY    AND    PATHOGENESIS  1 23 

has  been  much  controversy  as  to  whether  these  cells  are  leucocytes 
or  are  derived  from  the  fixed  tissue  elements.  Apart  from  a  few 
polymorphonuclear  leucocytes,  Wickman  considers  the  cells  to  be 
lymphocytes  or  lymphocytes  which  have  undergone  further  develop- 
ment. We  were  able  to  demonstrate  very  clearly  that  the  process 
is  a  different  one  from  that  which  occurs  in  true  suppurative  inflam- 
mation, in  the  course  of  the  examination  of  those  monkeys  in  which 
a  secondary  infection  had  unfortunately  taken  place  at  the  site  of 
inoculation.  The  cells  which  Wickman  regarded  as  being  derived 
from  lymphocytes  are  similar  to  the  "  polyblasts  "  of  Maximow. 
Instead  of  the  round  nucleus  with  much  chomatin  and  the  small 
amount  of  cytoplasm  which  characterize  the  true  lymphocyte,  these 
cells  have  a  nucleus  which  is  lighter  in  colour,  contains  less  chroma- 
tin, is  not  quite  round  but  slightly  folded,  and  a  wider  margin  of 
cytoplasm.  Wickman  found  cells  in  all  stages  intermediate  between 
the  true  lymphocyte  and  the  polyblast,  and  concluded  therefore  that 


4 

A- 


\v- 


Fig.  45. 


Infiltrated  vessel  in  the  cortex  of  monkey   No.    27    (from  the  side  opposite 
to  that  on  which  the  injection  was  made). 

the  latter  is  a  derivative  of  the  former.  The  polyblasts  are  specially 
numerous  in  tissue  infiltrations;  in  the  infiltrated  vessels  and  pia 
mater  the  true  lymphocyte  predominate  (vide  fig.  22).  In  neurono- 
phagy many  polymorphonuclear  leucocytes  as  well  as  polyblasts  are 
seen,  but  Wickman  considers  that  the  latter  alone  act  as  phagocytes. 

As  the  appearances  found  in  man  in  the  pia  mater,  spinal  cord, 
medulla,  brain,  &c,  correspond  almost  exactly  with  those  found  in 
the  monkey,  it  is  unnecessary  to  describe  them  in  detail.  I  refer 
the  reader  to  Wickman' s  description. 

In  man  and  in  the  monkey,  therefore,  the  so-called  poliomyelitis 
has  been  shown  to  be  a  non-suppurative,  infiltrative  inflammatory 
process  of  a  lymphocytic  type,  which  may  affect  the  pia  mater  or  any 
other  part  of  the  central  nervous  system  in  a  disseminated  manner, 
although  it  tends  to  involve  the  grey  matter,  and,  in  particular,  the 
anterior  horns 


124 


EPIDEMIC   INFANTILE   PARALYSIS 


Fig.  46. 
Infiltration  into  the  tissues  of  the  brain  of  monkey  Xo.  27. 


•  1  rJ*2^sS 


Fig.  47. 
Infiltration  of  a  vessel   (one  of  those  seen  in  fig.  44). 


PATHOLOGY    AND    PATHOGENESIS 


I2: 


The  Stage  Of  Repair.— I  was  able  to  study  this  stage  in  only 
one  instance.  Most  of  the  monkeys  which  became  paralysed  died 
in  a  few  days,  and  even  those  which  survived  the  first  few  days 
died  shortly  afterwards  with  symptoms  of  marasmus.  The  sole  excep- 
tion to  this  was  monkey  Xo.  t>7,  which  was  inoculated  on  March  2, 
1910.  Paralysis  set  in  on  the  9th,  and  speedily  became  complete  in 
the  hind  limbs.  The  monkey  died  (for  details  see  p.  57)  on  April  14, 
forty-three  days  after  inoculation  and  thirty-six  days  after  the  onset 


/ 


Fig.   48. 

The  greater  part  of  the  left  half  of  the  spinal  cord  of  monkey  No.   37. 
area  is  seen  at  the  apex  of  the  left  anterior  horn. 


An 


of  paralysis.  The  brain  was  not  examined.  No  lesions  were  found 
in  the  medulla,  the  cervical  or  the  dorsal  regions;  in  the  lumbar 
region  almost  symmetrical  lesions  were  present,  as  shown  in 
fig.  48,  although  the  magnification  is  low. 

Under  a  higher  power  the  lesion  is  seen  to  involve  the  greater 
part  of  the  anterior  horn  (.fig.  49),   particularly  in  its  lateral  part. 


126  EPIDEMIC  INFANTILE  PARALYSIS 

There  is  considerable  rarefaction  of  the  stroma,  the  wide  meshes  of 
which  are  filled  by  a  fine  network  containing"  small  collections  oi 
round  cells.  Ganglion  cells  are  almost  entirely  absent;  it  is  remark- 
able that  one  v/ell  preserved  cell  was  found  in  the  middle  of  the 
lesion.  I  have  been  unable  to  find  any  proliferation  of  the  blood- 
vessels, as  has  been  described  in  this  stage  by  several  authors.  In 
fig.  49  an  infiltrated  vessel  may  be  seen.  After  thirty-six  days,, 
therefore,  a  considerable  lesion  was  still  present  in  the  anterior 
horns,  but  nothing  of  the  nature  of  scar  tissue.  Judging  by  the 
clinical  history  of  the  acute  stage  of  the  illness,  and  by  the  appear- 
ances found  in  other  monkeys,  it  is  very  probable  that  other  and 
more  widespread  lesions  were  present  at  first,  which  had  disappeared 
with  the  exception  of  those  in  the  anterior  horns.     It  may  be  that 


r?;3» 


:--6l 


Fig.  49. 

The  anterior  horn  in  fig.  48  under  a  higher  power.  Chronic  changes ; 
rarefaction  of  the  stroma;  increased  number  of  cells;  to  the  right  a  blood- 
vessel with  infiltrated  walls ;  marked  destruction  of  the  ganglion  cells. 
Below  and  to  the  left  of  the  centre,  a  well  preserved  ganglion  cell. 

the  peculiar  liability  to  the  disease  of  this  part  of  the  spinal  cord 
is  shown  better  in  these  chronic  cases.  Levaditi  and  Stanesco  found 
scar  tissue  and  proliferation  of  the  blood-vessels  in  monkeys  which 
died  sixty-seven  days  after  the  onset  of  paralysis. 

According  to  the  more  exact  descriptions  of  the  stage  of  repair 
in  man,  particularly  in  those  given  by  Wickman,  the  lesions  are 
characterized  by  the  presence  of  cells  containing  fat  granules;  such 
cells  are  met  with  frequently  in  lesions  of  the  nervous  system,  they 
are  associated  with  degeneration  of  the  nervous  elements  and  are 
found  close  to  blood-vessels.  The  glia  cells  are  increased  in 
number  in  the  later  stages  of  repair.     It  has  been  shown  during  this. 


PATHOLOGY    AND    PATHOGENESIS  1 27 

stage  that  the  process  is  not  limited  to  the  anterior  horns,  but  takes 
place  extensively  in  Clarke's  column  and  in  the  posterior  horns. 
Degeneration  of  the  tracts  and  of  the  anterior  roots  has  been 
demonstrated  by  means  of  suitable  methods. 

In  all  the  monkeys  which  recovered  completely  from  the 
paralysis  we  were  unable  to  find  any  lesions.  It  is  true  that  these 
monkeys  were  only  killed  some  months  after  inoculation  and  several 
weeks  after  all  paralysis  had  disappeared.  Monkeys  which  were 
reinfected  without  any  result  after  they  had  recovered  from 
paralysis  showed  no  microscopical  lesions,  even  when  they 
were  examined  only  a  short  time  after  reinfection  (in  one  case 
eighteen  days). 

I  will  mention  here  certain  observations  which  have  been  made 
on  monkeys  killed  or  dying  during  the  stage  of  incubation.  In  my 
own  series  there  are  two  such  cases.  Monkey  No.  22  received  an  in- 
jection simultaneously  into  the  brain  and  peritoneum  on  January  18, 
1910;  it  died  of  gastro-enteritis  on  the  24th  before  any  paralysis  had 
appeared.  The  monkey  used  as  a  control  became  paralysed  on  the 
tenth  day.  Microscopical  examination  revealed  purely  normal  con- 
ditions. 

Monkey  Xo.  62  died  four  days  after  infection;  the  control 
became  paralysed  on  the  ninth  day.  Xo  lesions  were  found  in  the 
spinal  cord. 

Landsteiner  and  Levaditi  had  a  similar  experience  with  four 
monkeys  which  received  intracerebral  and  intraperitoneal  injections 
on  the  same  day.  Three  were  killed  on  the  second,  fourth,  and 
seventh  days  respectively.  The  fourth  became  paralysed  on 
the  eleventh  day.  The  central  nervous  system  of  the  first 
three  was  found  normal  except  that  there  was  a  slight  traumatic 
inflammation  of  the  meninges  in  the  case  of  the  two  killed  on  the 
second  and  fourth  days. 

In  the  light  of  these  experiments  it  seems  clear  that  lesions 
occur  only  just  before  the  onset  of  paralysis.  The  experience  of 
Leiner  and  v.  Wiesner  was  somewhat  different;  they  found  changes 
in  the  spinal  cord  (hypersemia,  small  haemorrhages,  degeneration  of 
the  g_anglion  cells)  on  the  third  day  after  infection;  the  control 
became  paralysed  on  the  eighth  day.  Whether  the  lesions,  which 
were  not  quite  typical,  were  really  due  to  the  virus  cannot  be  stated 
with  certainty.  Further  injections  made  with  material  from  this 
spinal  cord  into  other  monkeys  wTere  not  successful.  The  cord  of  a 
monkey  killed  on  the  fifth  day  was  proved  to  contain  virus. 

The  Final  Stage. — This,  the  stage  of  scar  formation,  I  have 
not  been  able  to  observe  from  reasons  which  I  have  given  above. 
In  man  a  scar  occupies  the  anterior  horns  usually,  and  makes  them 
appear  diminished  in  size.  Under  the  microscope  this  scar  appears 
to  be  composed  of  fibrillar  sclerotic  tissue  with  no  nervous  elements. 
In  other  cases  the  only  change  seen  is  atrophy  of  the  ganglion 
cells;  Charcot's  theory  of  a  primary  cell  lesion  was  probably  based 
on  such  cases.       The  blood-vessels  are  thickened  in  the   sclerotic 


128  EPIDEMIC   INFANTILE   PARALYSIS 

areas.  The  anterolateral  tracts  show  some  degeneration;  much 
importance  was  attached  to  this  change  by  the  earlier  investigators 
whose  attention  was  thus  turned  away  from  the  more  important 
lesions.  This  degeneration  of  the  lateral  tract  must  not  be  regarded 
as  evidence  that  the  process  had  invaded  the  white  matter,  but  as 
an  endogenous  degeneration.  It  is  seen  at  levels  where  the  grey 
matter  is  normal.  In  rare  instances  it  may  be  due  to  small  lesions 
in  the  white  matter.  Degeneration  and  atrophy  of  the  peripheral 
nerves  and  muscles  are  present.  Finally,  there  are  traces  of  atrophy 
in  the  cerebral  motor  area;  this  is  probably  a  secondary  result  of 
the  destruction  of  the  lower  motor  neuron.  Wickman,  however, 
has  reminded  us  that  the  effect  of  the  cerebral  lesions  must  not  be 
overlooked,  and  our  experience  with  monkeys  has  shown  that 
lesions  are  specially  liable  to  occur  in  the  central  convolutions. 

Poliomyelitis  in  Adults,  Landry's  Paralysis,  Polyneuritis, 
Rabies  and  Borna's  Disease  in  their  Relation  to  Heine-Medin 
Disease. — I  have  already  mentioned  the  important  contributions  to 
our  knowledge  of  the  nature  of  Heine-Medin  disease  which  have 
resulted  from  the  investigations  into  the  pathology  of  the  disease 
by  Wickman  and  others.  Wickman  was  the  first  to  demonstrate 
afresh  the  complete  identity  of  poliomyelitis  in  adults  and  infantile 
poliomyelitis;  he  showed  that  Landry's  paralysis  and  poliomyelitis 
acuta  are  identical  from  the  point  of  view  of  their  pathology,  and 
produced  evidence  which  made  it  probable  that  their  etiology  is  the 
same  also.  By  means  of  a  critical  analysis  he  showed  that  in  many 
instances,  from  purely  clinical  reasons,  the  term  polyneuritis  is 
used  for  cases  which  are  caused  de  facto  by  a  poliomyelitis.  The 
clinical  symptoms  (parsesthesiae,  pains,  &c.J  can  be  explained  by  a 
poliomyelitic  lesion,  and  the  good  prognosis  which  attaches  to 
"  polyneuritis  "  is  not  incompatible  with  a  poliomyelitic  process. 
As  Striimpell  suggested  a  long  time  ago,  Wickman  considers  that 
the  differentiation  between  polyneuritis  and  poliomyelitis  is  more  or 
less  artificial.  In  Chapter  II  we  have  seen  how  important  a  recog- 
nition of  this  fact  is  for  clinical  work. 

Wickman 's  observations  on  the  similarity  of  the  pathological 
picture  in  poliomyelitis  and  rabies  has  shown  the  way  in  regard  to 
studies  into  the  etiology  of  Heine-Aledin  disease.  The  pathological 
process  in  rabies  is  a  disseminated,  infiltrative  myelitis,  which  shows 
a  preference  for  attacking  the  blood-vessels  and  particularly  the 
anterior  horns. 

Again,  Joest  and  Degen  have  shown  that  the  so-called  Borna's 
disease  in  horses  presents  an  almost  complete  pathological  analogy 
to  Heine-Medin  disease  in  man.  In  that  disease  they  found  a  dis- 
seminated, infiltrative  meningo-myelo-encephalitis  of  a  lvmphocytic 
type,  which  specially  affected  the  blood-vessels.  The  only  difference 
between  it  and  infantile  paralysis  lies  in  the  fact  that  it  tends  rather 
to  involve  the  brain,  by  preference  the  olfactory  lobe.  But  it  also 
affects  the  rest  of  the  central  nervous  system,  and  in  the  spinal  cord 
the  anterior  horns  are  a  favourite  situation.     In  other  particulars 


PATHOLOGY    AND    PATHOGENESIS  1 29 

the  pathological  features  are  very  similar  (slight  macroscopic 
changes,  involvement  of  the  meninges,  relation  to  the  blood-vessels, 
the  condition  of  the  cerebrospinal  fluid).  I  have  already  mentioned 
the  bodies  which  Joest  and  Degen  found  in  the  ganglion  cells,  and 
which  they  regard  as  specific  to  Borna's  disease.  It  would  be  not 
uninteresting  to  investigate  {e.g.,  by  means  of  serum  diagnosis)  the 
biological  relationship  between  the  virus  of  Heine- Aledin  disease 
and  that  of  Borna's  disease.  I  stated  in  Chapter  III  that  horses 
are  not  susceptible  to  the  virus  of  Heine-Aledin  disease. 

IV PATHOGENESIS. 

In  the  first  section  of  this  chapter  I  gave  a  summary  of  the 
historical  aspect  of  the  pathology  and  pathogenesis  of  the  disease; 
I  also  formulated  four  questions.  Having  sketched  the  progress 
which  has  been  made  by  experiments  on  animals,  I  will  attempt  to 
provide  answers  to  these  questions. 

The  Point  of  Attack  of  the  Virus. — At  what  point  in  the  central 
nervous  system  does  the  virus  first  have  an  effect  ?  Controversy  has 
raged  around  the  question  whether  the  ganglion  cell  is  affected 
primarily,  as  Charcot  believed,  or  whether  the  first  change  is  an 
interstitial  one,  according  to  the  suggestion  made  by  Roger  and 
Damaschino.  Such  a  controversy  is  perfectly  natural.  On  the 
one  hand,  Charcot's  theory  explained  the  clinical  symptoms  which 
in  great  part  point  to  a  purely  motor  paralysis.  Such  a  selective 
action  of  the  virus  was  not  a  new  idea;  we  were  accustomed  to  it  in 
the  case  of  tetanus.  On  the  other  hand,  pathological  investigation 
showed  not  only  that  the  lesion  was  not  purely  degenerative,  but 
that  it  was  by  no  means  confined  to  the  motor  regions  of  the  cord. 
In  that  case  how  was  the  motor  character  of  the  paralysis  to  be 
explained  ?  Further ,  accepting  the  fact  that  the  pathological  pro- 
cess mainly  affected  the  motor  regions,  why  should  a  virus  which 
acted  by  producing  disseminated  lesions  show  this  preference  for 
the  anterior  horns  ? 

Keeping  to  the  microscopical  appearances,  the  interstitial 
character  of  the  process  appears  to  be  very  well  marked.  The 
involvement  of  the  blood-vessels  is  so  striking  that  in  many  cases 
one  may  say  that  the  distribution  of  the  lesions  depends  mainly  upon 
the  vascular  supply  and  particularly  upon  the  situation  of  the  veins. 
The  question  arises,  whether  the  disease  of  the  vessels  may  not  be 
explained  by  some  pathological  process  affecting  the  ganglion  cells 
or  glia,  and  secondarily  acting  as  an  irritant  to  the  vessels,  causing 
emigration  of  the  lymphocytes.  In  such  a  case,  an  accumulation  of 
lymphocytes  around  the  blood-vessels  would  be  a  natural  sequence. 
Against  this  view,  however,  the  observations  made  by  Wickman 
and  ourselves  on  the  kind  of  vessel  involved  are  of  much  importance. 
According  to  the  theory,  the  smallest  vessels,  the  capillaries,  should 
be  the  most  affected,  but  we  find  it  to  be  the  veins.  Further,  well 
preserved  ganglion  cells  are  often  seen  in  the  middle  of  a  markedlv 

9 


I30  EPIDEMIC   INFANTILE  PARALYSIS 

infiltrated  area  and  even  quite  close  to  veins  which  are  severely 
affected.  There  is  little  justification  for  supposing"  that  the  cells 
are  really  damaged,  but  that  this  cannot  be  seen,  because  slight 
changes  in  the  cells  are  so  easily  recognized.  It  is  therefore  impos- 
sible to  believe  that  the  involvement  of  the  vessels  is  secondary  to 
an  affection  of  the  nervous  elements.  The  finding  of  infiltrated 
vessels  in  the  middle  of  the  white  matter,  at  a  distance  from  the 
grey  matter,  is  another  argument  for  the  primary  nature  of  the 
lesion  in  the  vessels;  so  also  is  the  presence  of  lesions  in  the  pia 
mater,  particularly  when  they  are  found  on  the  posterior  aspect 
of  the  cord,  far  from  the  grey  matter,  and  at  levels  in  the  cord 
where  the  grey  matter  is  scarcely  involved  at  all.  Everything 
points  to  the  change  in  the  vessels  being  largely  independent  of 
changes  in  the  nervous  elements;  there  is  no  doubt  that  in  at  any 
rate  very  many  places  we  arc  justified  in  considering  tlic  lesion  to  be 
primarily  vascular  or  perivascular. 

But  this  does  not  mean  that  the  virus  attacks  the  vessels  alone 
and  has  no  direct  effect  upon  the  ganglion  cells.  The  general 
impression  is  that  the  changes  in  the  ganglion  cells  are  of  a  secon- 
dary nature;  it  may  be  that  the  infiltrative  process  extends  directly 
from  the  vessels  to  the  ganglion  cells,  or  that  the  cells  succumb  to 
nutritional  disturbances  resulting  from  the  diseased  condition  of  the 
vessels  or  from  the  oedema.  The  argument  drawn  from  clinical 
experience,  that  the  occurrence  of  paralysis  so  suddenly  can  be 
explained  only  by  a  primary  affection  of  the  ganglion  cells,  cannot 
be  maintained;  the  experiments  on  monkeys  have  shown  that  inter- 
stitial change  is  very  considerable  in  those  cases  where  paralysis 
sets  in  suddenly  and  rapidly  causes  death.  Demonstrable  lesions  in 
the  interstitial  tissues  may  occur  therefore  quite  as  rapidly  as  in  the 
parenchyma.  I  again  call  particular  attention  to  the  absence  of  any 
lesion  shortly  before  the  onset  of  paralysis  in  monkeys.  Some- 
times, it  is  true,  the  ganglion  cells  appear  to  be  the  only  structures 
involved ;  but  in  my  opinion  enough  importance  is  not  attached  to 
the  oedema  which  is  frequently  present  in  such  cases.  One  fact 
proves  conclusively  that  primary  affection  of  the  ganglion  cells  may 
occur;  that  is  the  neuronophagy  which  is  seen  in  the  most  acute  cases. 
Although  here  interstitial  changes  are  by  no  means  absent,  yet  the 
isolated  cells  surrounded  by  round  cells  give  the  impression  of  a 
localization  of  the  damage  to  the  ganglion  cell.  Landsteiner  and 
Levaditi  observed  degenerative  change  in  the  cells  before  the 
occurrence  of  neuronophagy,  but  I  was  unable  to  find  it.  I  believe 
that  this  type  of  alteration  in  the  cell  is  not  followed  by  neurono- 
phagy and  is  caused  indirectly.  I  saw  quite  normal  cells  surrounded 
by  lymphocytes.  Nor  could  I  convince  myself  that  the  interstitial 
changes  were  preceded  by  recognizable  alterations  in  the  ganglion 
cells,  as  has  been  reported  by  Landsteiner  and  Levaditi.  and  on 
which  they  base  their  argument  that  the  process  always  begins  in 
the  ganglion  cells.  [They  quite  recognize  that  the  changes  in  the 
vessels  and  the  pia  may  appear  independently.]      On  the  contrary,  I 


PATHOLOGY    AND    PATHOGENESIS  131 

have  frequently  seen  well  preserved  ganglion  cells  lying  within  the 
infiltrated  areas.  In  the  atypical  (marantic)  forms  of  the  disease 
Leiner  and  v.  Wiesner  found  no  cell  infiltration  but  hyperaemia, 
haemorrhages  and  degeneration  of  the  ganglion  cells.  In  discussing 
the  pathogenesis  of  the  typical,  paralytic  form  of  the  disease  it 
seems  to  me  to  be  an  important  observation  that  the  non-paralytic 
form  presents  appearances  indicative  of  essential  involvement  of  the 
ganglion  cells. 

The  general  conclusion  arrived  at  is  this  :  The  process  is  mainly 
primarily  interstitial;  the  ganglion  cells  are  affected  primarily  in 
some  degree,  but  this  is  small  compared  with  the  interstitial  change. 
Our  position  is  the  same  as  that  taken  up  by  Fr.  Schultze  many 
years  ago   on  the   basis   of   histological   and   critical   studies. 

Having  arrived  at  this  point,  as  Wickman  rightly  says,  the 
•difficulty  in  explaining  the  clinical  symptoms  really  begins.  One 
would  expect  from  the  microscopical  appearances  to  find  the  clinical 
picture  of  a  transverse  myelitis;  instead  of  which  the  symptoma- 
tology is  that  of  a  system  disease  of  the  spinal  cord.  The  in- 
congruity between  the  symptoms  and  the  pathological  findings  has 
.given  much  trouble  to  the  adherents  of  the  primary  vascular  theory. 
Many  hypotheses  have  been  suggested,  which  all  depend  upon  some 
-cause  outside  the  nervous  parenchyma  to  explain  the  peculiar 
susceptibility  of  the  anterior  horns.  This  liability  of  the  anterior 
horns  is  a  fact  admitting  of  no  doubt.  A  point  of  special  import- 
ance arising  out  of  the  experimental  work  is  the  fact  that  in  mon- 
keys which  were  inoculated  intracerebrally  the  favourite  situation 
of  the  pathological  process  was  in  the  grey  matter  of  the  anterior 
horns  of  the  spinal  cord;  the  symptoms  were  mainly  those  of  a 
flaccid  motor  paralysis,  usually  of  the  hind  limbs,  and  so,  in  spite 
of  the  abnormal,  artificial  point  of  entry  of  the  virus,  the  appear- 
ances presented  by  human  "  spinal  "  paralysis  were  reproduced 
with   considerable   fidelity.     How   can   this   be   explained  ? 

In  view  of  the  special  involvement  of  the  blood-vessels  it  has 
heen  suggested  that  peculiarities  of  the  vascular  supply  are  the 
■cause  of  the  remarkable  vulnerability  displayed  by  the  anterior 
horns.  The  area  of  distribution  of  the  anterior  spinal  artery  was 
said  to  be  particularly  liable;  Kadyis  had  shown  that  it  supplied 
the  anterior  horns  by  branches  which  passed  into  the  cord  at  the 
"bottom  of  the  anterior  longitudinal  fissure  and  then  turned  out- 
wards. Pierre  Marie  stated  in  consequence  of  this,  that  the  whole 
process  was  one  of  embolism  of  the  anterior  spinal  artery.  Wick- 
man has  shown  that  this  supposition  is  certainly  incorrect.  Apart 
from  the  fact  that  no  embolism  or  thrombosis  is  found  in  the  vessel 
the  character  of  the  lesion  does  not  suggest  that  it  is  of  embolic 
origin;  no  necrosis  is  seen.  Again,  embolism  artificially  produced 
shows  no  tendency  to  affect  the  grey  matter  more  than  any  other 
part.  Further,  it  has  been  seen  that  not  the  arteries  but  the  veins 
are  the  more  affected  and,  finally,  the  process  is  by  no  means 
confined  to  the  central  regions  of  the  cord;  the  peripheral  portions 


I32  EPIDEMIC   INFANTILE   PARALYSIS 

are  hardly  less  affected.  For  these  and  other  reasons  the  theory 
of  embolism  must  be  rejected,  and  no  cause  operating"  by  way  of 
the  anterior  spinal  artery  alone  can  be  accepted.  Wickman's  theory 
is  worthy  of  more  consideration;  he  associates  together  the  vulner- 
ability and  the  vascularity  of  the  different  parts  of  the  cord.  The 
greater  the  blood  supply  is,  the  more  intense  the  pathological 
process.  When  the  arrangement  of  vessels  changes  the  localization 
of  the  lesions  is  found  to  change  also;  in  the  lower  lumbar  regions 
the  lesions  are  found  mainly  in  the  anterior  horns,  but  in  the  upper 
lumbar  and  lower  dorsal  regions  the  process  is  more  in  the  region 
of  Clarke's  column,  which  at  this  level  is  much  more  richly  supplied 
with  blood-vessels.  I  shall  return  later  to  certain  difficulties  which 
even  Wickman's  theory  does  not  explain. 

The  Spread  of  the  Virus  within  the  Central  Nervous  System. — 
The  microscopical  appearances  indicate  that  the  vessels  constitute 
the  main  channel  along  which  the  virus  spreads.  Wickman  holds 
that  the  clinical  symptoms  contra-indicate  this  route;  there  is  a 
certain  regularity  in  the  way  the  paralysis  spreads  which  indicates 
that  the  pathological  process  underlying  it  is  advancing  in  a  con- 
tinuous if  rapid  manner.  This  continuity  of  spread  of  the  lesion 
is  shown  in  microscopical  sections  (compare  the  photographs  of 
longitudinal  sections),  and  leads  one  to  suspect  the  lymph  channels. 
Experimental  studies  have  shown  that  the  virus  has  a  special  affinity 
to  the  lymphatics,  and  Wickman  has  shown  that  in  the  central 
nervous  system  the  blood-vessels  are  surrounded  by  perivascular 
lymph  channels  in  which  the  first  signs  of  a  lesion  appear.  Further, 
the  lymph  channels  which  lie  in  the  nervous  matter  itself  must  be 
considered.  Some  of  the  observations  made  on  monkeys  have  a 
bearing  on  this  point;  after  intracerebral  inoculation  into  the  central 
convolutions  on  one  side,  the  paralysis  appeared  usually  on  the 
contralateral  side.  This  leads  me  to  the  difficult  question  of  ex- 
plaining how  it  is  that  monkeys  when  inoculated  into  the  brain 
suffer  subsequently  from  paralysis  which  is  mainly  spinal.  I 
imagine  that  the  virus  passes  along  the  perineural  lymph  spaces 
as  well  as  the  perivascular  ones;  on  reaching  certain  regions  in 
the  spinal  cord  which  are  richly  supplied  with  lymph  (the  grey 
anterior  horns)  it  finds  there  a  particularly  suitable  soil.  The 
objection,  that  there  is  plenty  of  opportunity  for  the  virus  to 
develop  in  the  brain  itself,  is  not  justifiable;  in  the  first  place, 
cerebral  lesions  are  certainly  more  common  in  monkeys  which  have 
received  an  intracerebral  inoculation  than  in  man;  in  the  second 
place,  the  motor  cells  in  the  brain  have  not  the  same  close  relation 
to  the  blood-vessels  which  is  found  within  the  narrow  limits  of 
the  spinal  cord,  with  its  complex  network  of  vessels.  While  I 
agree  with  Wickman  that  richness  in  vascular  and  lymphatic  supply 
causes  the  peculiar  liability  of  the  anterior  horns,  I  am  inclined  to 
explain  the  predominance  of  spinal  symptoms  in  monkeys  which 
have  received  intracerebral  inoculation  by  the  direct  passag'e  of 
the  virus  along  the  perineural  lymph  spaces  down  to  the  anterior 


PATHOLOGY    AND    PATHOGENESIS  1 33 

horn  of  the  opposite  side,  where  it  finds  a  soil  suitable  for  its 
further  development.  Joest's  observations  on  Borna's  disease  lend 
some  support  to  this  view;  he  found  the  most  severe  lesions  in 
the  olfactory  lobe  and  connects  this  with  the  entrance  of  the  virus 
through  the  nose.  In  Borna's  disease  the  virus  spreads  along"  the 
perivascular  and  perineural  lymphatics,  and  finally  becomes  localized 
in  the  anterior  horns  of  the  grey  matter  of  the   cord. 

In  short,  the  virus  spreads  along  the  lymph  channels  in  the 
central  nervous  system,  along  those  which  surround  the  vessels 
as  zvell  as  those  running  in  the  substance  of  the  brain  and  spinal 
cord.  The  virus  develops  more  freely  zvherever  there  is  a  rich 
supply  of  lymph. 

Hoche  assumes  that  the  central  canal  serves  as  a  channel  for 
the  virus.  His  theory  is  founded  upon  experimental  evidence,  and 
he  considers  that  the  patency  of  the  canal  in  children  is  the  cause 
of  the  frequency  with  which  they  suffer  from  the  disease.  This 
explanation  cannot  be  accepted.  In  the  first  place,  the  poliomyelitis 
of  adults,  in  whom  the  central  canal  is  closed,  is  quite  similar  to 
that  of  children,  and  in  the  second  place  the  central  canal  is  only 
rarely  involved  in  human  beings  and  never  in  monkeys,  according 
to  my  own  experience. 

The  Route  by  which  the  Virus  reaches  the  Spinal  Cord. — 
At  first  sight,  considering  how  extensively  the  vessels  are  affected, 
it  seems  as  though  the  virus  must  have  been  brought  to  the  cord 
by  the  blood-stream.  However,  Wickman  has  shown  that  it  is  not 
the  capillaries,  as  one  would  expect  in  such  a  case,  but  the  veins 
which  are  principally,  and  sometimes  exclusively,  involved.  That 
the  blood  and  the  organs  rich  in  blood  contain  no  virus,  or  at  most 
the  minutest  quantity,  is  strong  evidence  against  the  theory  of 
hematogenous  infection.  Virus  has  never  been  found  in  the  blood 
during  the  stage  of  incubation.  The  following  observation  made 
by  Renault  is  further  evidence  against  this  possible  method  of 
transmission  of  the  virus  :  A  pregnant  woman  had  a  severe  attack 
of  poliomyelitis,  recovered,  went  to  term  and  bore  a  healthy  child 
with  no  signs  of  paralysis.  As  the  virus  is  capable  of  passing 
through  the  most  perfect  filters  known,  one  would  expect  that  it 
would  be  transmitted  to  the  foetus,  if  it  circulated  in  the  blood- 
stream. It  has  been  clearly  shown  by  experiment,  that  inoculation 
into  nerves  is  commonly  successful,  the  virus  passing  up  within 
the  nerve  to  the  spinal  cord  and  causing  paralysis  of  the  muscles 
supplied  by  that  nerve.  Further,  it  has  been  demonstrated  that 
there  is  a  definite  relationship  between  the  situation  chosen  for 
inoculation  and  the  part  of  the  spinal  cord  which  is  first  affected; 
the  virus  always  chooses  the  shortest  way  to  the  cord,  i.e.,  the  path 
of  the  nerves. 

On  page  ioo  I  have  shown  that  the  occasional  success  attending 
intravenous  inoculation  does  not  contradict  the  theory  of  trans- 
mission by  the  nerves.  Consequently  the  conditions  are  almost 
exactly  those  which  obtain  in  the  case  of  rabies.      [Some  authors 


134  EPIDEMIC  INFANTILE   PARALYSIS 

recently  have  revived  the  hematogenous  theory  for  rabies,  on  the 
ground  that  the  lesions  first  observed  are  vascular  in  type;  the 
above  critical  analysis  makes  it  clear  that  this  is  no  valid  argument 
in  favour  of  transmission  by  the  blood-stream.] 

Harbitz  and  Scheel,  as  well  as  Flexner,  accept  the  suggestion 
made  by  Schultze  a  long  time  ago,  that  the  virus  first  settles  in 
the  meninges  and  then  causes  the  lesions  in  the  cord  by  direct 
extension  of  the  meningitic  lesion.  According  to  our  views,  it  is 
quite  possible  and  probable  that  the  virus,  proceeding  along  the 
nerves,  first  reaches  the  pia  mater  and  gives  rise  to  lesions  in  it. 
But  that  the  spinal  cord  is  affected  only  directly  from  the  meninges 
seems  to  us,  as  it  does  to  Wickman,  exceedingly  unlikely;  there 
is  no  exact  correspondence  between  the  lesions  in  the  pia  and  those 
in  the  cord,  and  the  pia  in  the  depths  of  the  anterior  fissure  is 
usually  more  affected  than  that  covering  the  exterior  of  the  cord. 
It  is  by  no  means  rare  to  find  the  infiltration  of  the  fold  of  pia 
cease  when  the  pia  reaches  the  surface  of  the  cord.  If  we  bear 
in  mind  the  knowledge  gained  from  experiments,  that  the  virus 
tends  to  follow  the  lymph-stream,  we  shall  not  be  far  wrong  in 
saying  that  the  virus  of  Heine-Medin  disease  travels  centripetally 
in  the  lymphatics  lying  round  and  in  the  peripheral  nerves  until  it 
readies  tJie  central  nervous  system,  where  it  attacks  the  pia  mater 
and  simultaneously  gains  entrance  into  the  cord  along  the  spinal 
roots. 

Joest's  observations  on  Borna's  disease  in  horses  give  valuable 
support  to  this  view.  After  a  most  careful  consideration  of  all 
the  probable  paths  along  which  the  virus  could  travel  he  arrives 
at  the  conclusion  that  the  active  agent  reaches  the  brain  by  way 
of  the  interstices  and  the  sheath  of  the  nerves.  In  Borna's  disease 
infection  begins  in  the  nasal  mucous  membrane ;  hence  the  early 
and  intense  involvement  of  the  olfactory  lobe.  The  virus  passes 
in  a  centripetal  direction  to  the  subarachnoid  space,  causes  a  certain 
amount  of  meningeal  irritation,  and  then  passes  along  the  nerve 
into  the  brain.  Joest  denies  that  the  further  extension  of  the 
process  within  the  central  nervous  system  is  due  to  direct  involve- 
ment from  the  pia  mater. 

The  Portal  of  Entry  of  the  Virus. — The  initial  symptoms  of 
the  disease  point  to  the  mouth  and  throat  and  the  respiratory  tract 
or  to  the  alimentary  tract  as  the  situations  where  the  virus  enters 
the  body.  The  occurrence  of  lesions,  which  are  clearly  due  to  the 
virus,  in  the  gastro-intestinal  tract  after  inoculation  by  any  method 
and  the  appearance  of  the  virus  in  the  mucous  membrane  of  the 
throat  under  the  same  condiions,  lead  one  to  believe  that  these 
symptoms  are  the  result  of  a  secondary  inoculation  with  the  virus. 
But  since  these  symptoms  almost  invariably  precede  an  attack  of 
Heine-Medin  disease  in  human  beings,  I  cannot  but  think  that  they 
are  symptoms  of  primary  infection.  The  experimental  results  do 
not  put  these  situations  out  of  court  as  points  of  entry  of  the  virus, 
although  it  is  not  easy  to  produce  infection  by  these  routes.     In 


PATHOLOGY    AND    PATHOGENESIS  135 

consideration  of  the  known  predilection  of  the  virus  for  lymphatic 
tissue,  it  is  quite  probable  that  the  mucous  membranes  of  the  throat 
and  of  the  intestinal  canal  constitute  the  chief  portals  of  entry  of 
the  virus  because  they  are  so  richly  provided  with  lymphatics.  It 
is  difficult  to  say  which  of  the  two  is  the  more  common  portal. 
Different  epidemics  differ  in  this  respect.  If  our  theory  is  correct, 
that  the  virus  always  takes  the  shortest  route  to  the  central  nervous 
system,  we  are  inclined  to  consider  the  gastrointestinal  tract  as 
the  main  point  of  entry,  because  the  large  majority  of  cases  are 
affected  in  the  lower  limbs.  The  fact  that  the  lower  limbs  are 
usually  affected,  wherever  inoculation  has  taken  place,  must  not  be 
ignored.  In  future,  therefore,  it  will  be  of  the  greatest  importance 
to  notice  carefully  where  paralysis  first  shows  itself.  Particularly 
it  must  be  noted  whether  cases,  which  have  symptoms  first  in  the 
mouth  and  throat,  develop  paralysis  first  in  the  upper  limbs.  It 
would  not  be  remarkable  if  such  cases  ultimately  were  affected  in 
the  lower  limbs  more  than  in  the  upper,  because  we  know  that  the 
segments  of  the  spinal  cord  which  correspond  to  the  lower  limbs 
are  so  much  more  easily  affected  than  the  rest  of  the  segments. 
It  is  improbable  that  the  virus  often  enters  through  the  nasal 
mucous  membrane,  because  the  cerebral  forms  of  the  disease  are 
rare. 

Conclusions. — None  of  the  deductions  we  have  drawn  can  be 
considered  conclusive.  In  the  natural  sciences  it  is  rare  to  find 
a  certainty.  Many  steps  in  our  arguments  are  based  on  hypotheses. 
The  following  is  the  most  probable  of  all  the  theories  advanced 
to  explain  the  pathogenesis  of  the  disease. 

The  virus  enters  the  body  by  way  of  the  lymphatics  of  the 
throat  or  of  the  intestinal  tract,  or  of  both  (this  varies  in  different 
epidemics).  Thence  it  passes  in  the  lymphatics  within  or  around 
the  peripheral  nerves  to  the  spinal  cord.  Here  it  causes  slight 
infiltrative  inflammation  of  the  pia  mater,  and  then  enters  the  cord 
along-  the  spinal  roots.  It  spreads  within  the  cord  chiefly  along 
the  lymph  spaces  round  the  veins,  but  also  in  those  lying  in  the 
nervous  tissues  themselves.  It  develops  freely  in  parts  of  the 
cord,  such  as  the  anterior  horns  of  the  grey  matter,  in  which  the 
vascular  and  consequently  the  lymph  supply  is  rich  and  where  the 
texture  of  the  tissues  is  loose.  Here  the  virus  gives  rise  to  in- 
filtrative inflammation  of  the  lymphocytic  type,  which  causes 
degeneration  and  destruction  of  the  ganglion  cells  either  by  inter- 
ference with  the  nutrition  of  the  cells,  or  by  direct  involvement 
in  the  infiltrative  process.  In  other  cases,  particularly  those  in 
which  the  process  is  very  acute,  the  ganglion  cells  are  affected 
primarily,  the  cells  being  always  destroyed  by  the  action  of 
phagocytes  which  are  usually  lymphocytes. 


CHAPTER  V. 

Epidemiology. 


I.— HISTORY  OF  THE  EPIDEMICS. 

Early  Reports.— The  disease  has  certainly  existed  for  a  very- 
long"  time.  Heine  mentions  patients  who  had  suffered  from  the 
disease  more  than  fifty  years  before  his  time;  he  says  that  the 
disease  "  is  not  rare  "  and  quotes  an  author,  Shaw,  who  met  with 
it  in  India,  Egypt,  and  other  extra-European  countries.  "  Another 
author,  Colman,"  writes  Heine,  "'  even  mentions  an  epidemic." 
Wickman  considers  that  this  latter  statement  requires  considerable 
reservation;  an  author  named  Colmer  (not  Colman)  reported  that 
he  had  heard  from  the  mother  of  a  child  suffering  from  hemiplegia, 
that  several  cases  of  hemiplegia  and  paraplegia  in  children  had 
occurred  in  the  district  within  a  space  of  three  or  four  months. 
The  report  therefore  contains  little  that  is  of  value  as  evidence. 

It  is  curious  that  the  older  literature  contains  not  a  single 
reference  to  any  epidemic,  although  infantile  paralysis  most  cer- 
tainly occurred.  After  the  appearance  of  Heine's  monographs,  and 
at  a  time  when  the  literature  of  the  disease  was  becoming  extensive, 
no  mention  was  made  of  any  epidemic  before  1880.  It  may  have 
been  because  small  groups  of  cases  were  not  recognized  as  such, 
owing  to  the  infectivity  of  the  disease  being  unknown,  or  because 
the  clinical  differences  between  the  cases  caused  them  to  be 
regarded  as  examples  of  different  diseases.  But  when  the  sym- 
ptomatology of  the  commonest  type  of  the  disease  had  been  fully 
described  under  the  name  of  spinal  "  infantile  paralysis,"  the 
absence  of  reports  of  epidemics  can  be  explained  only  by  the  fact 
that  such  epidemics  did  not  occur  before  1880. 

The  Scandinavian  authors  were  the  first  to  draw  attention  to 
the  epidemic  occurrence  of  the  disease.  At  about  the  same  time 
reports  were  received  from  other  countries  concerning  groups  of 
cases  and  the  occurrence  of  several  cases  in  one  family.  The 
following  is  a  short  summary  of  the  epidemics  recorded  in  the 
different  countries. 

Sweden  and  Norway. — These  two  countries  dispute  one 
another's  claim  to  priority  in  the  matter  of  recording  the  first 
epidemic.      Xetter    states    that    a    Norwegian    author,     Ch.     Bull, 


EPIDEMIOLOGY  137 

recorded  a  small  epidemic  of  fourteen  cases,  four  of  which  were 
fatal,  in  the  year  1868;  Bull  is  said  to  have  called  the  disease 
"meningitis  spinalis  acuta,"  but  to  have  described  it  so  that  there 
can  be  no  doubt  of  its  being  infantile  paralysis.  Unfortunately  I 
have  not  been  able  to  read  the  report.  The  epidemic  lasted  from 
May  to  August,  and  reached  its  climax  in  July,  when  eight  cases 
occurred.  According  to  Wickman,  the  Swedish  physician  Bergen- 
holtz  was  the  first  to  report  an  epidemic  in  1881 ;  he  described 
eighteen  cases  from  Umea  in  the  north  of  Sweden.  In  this  case 
there  is  no  doubt  of  the  disease  being  Heine-Medin  disease.  The 
epidemic  remained  unknown,  as  the  report  was  only  sent  to  the 
local  health  authorities.  The  observations  of  Oxholm  (Norway) 
and  Cordier  (France)  also  passed  unnoticed;  they  include  some  state- 
ments pointing  to  an  epidemic  outbreak  of  the  disease. 

Medin  first  made  widely  known  the  epidemic  which  he  observed. 
He  published  his  exhaustive  clinical  studies  on  forty-three  cases 
which  occurred  in  and  near  Stockholm  during  the  months  May  to 
November,  1887,  and  on  twenty-one  cases  which  came  under  his 
notice  in  1895.  The  subsequent  epidemics  in  Sweden  were  studied 
very  thoroughly.  Wickman  obtained  unexampled  experience 
during  the  epidemics  of  1899  (fifty-four  cases  in  Stockholm),  1903 
(twenty  cases  in  Goteborg),  and  1905-1906  (about  1,100  cases  spread 
over  a  great  part  of  Sweden).  His  description  has  become  a  classic. 
During  the  years  1907  and  1908  many  more  cases  were  reported 
from  Sweden. 

Oxholm  observed  a  small  epidemic  of  five  cases  in  1886.  It  is 
doubtful  if  he  recognized  the  true  nature  of  the  disease.  In  the 
same  year  Leeg'.aard  reported  a  small  epidemic  in  Mandal,  a  small 
Norwegian  town.  In  1893  Bulow-Hansen  and  Harbitz  made  a 
careful  pathological  examination  of  three  cases  which  occurred  in 
one  family.  Looft  observed  a  small  epidemic  in  1898-99  in  Bergen. 
The  first  large  epidemic  in  Norway  took  place  from  July  to  October, 
1899,  fifty-four  cases  in  Bratsberg-,  which  were  studied  by  Leegaard. 
On  this  occasion  he  made  the  remarkable  discovery  that  the 
infection  spread  along  the  lines  of  traffic.  In  1904  Nannestad 
examined  forty-one  cases  and  Platou  twenty-four. 

Finally,  at  the  same  time  as  the  great  Swedish  epidemic,  about 
1,000  cases  occurred  in  Norway  in  1905-06  (Leegaard,  Harbitz  and 
Scheel,  Geirsvold,  &c). 

Assuming  that  earlier  epidemics  had  not  occurred  unnoticed,  a 
gradual  increase  is  found,  from  1880  onwards,  in  Scandinavia.  At 
first  only  small  groups  of  cases,  some  in  families,  were  noticed,  then 
small  endemic  outbreaks,  later  a  true  epidemic  in  Sweden  in  1887, 
still  later  a  larger  epidemic  in  both  countries  in  1899,  and.  finally, 
a  big  epidemic  over  a  great  part  of  Scandinavia  in  1905.  In  propor- 
tion to  the  population  this  was  certainly  the  most  serious  epidemic. 
The  progress  of  the  epidemics  is  comparable  to  that  of  the  North 
American  prairie  fires,  which  begin  with  a  small  outbreak,  spread 
insidiously,  and  finally  burst  into  a  mighty  conflagration. 


ISO  EPIDEMIC   INFANTILE   PARALYSIS 

Germany. — The  epidemics  in  Germany  have  followed  on  similar 
lines. 

In  1882,  Mobius  and  Sanger  saw  a  brother  and  sister,  one  of 
whom  suffered  from  the  spinal,  and  the  other  from  the  cerebral 
form  of  the  disease. 

Striimpell  observed  three  cases  in  one  month  in  1886;  two  of 
the  cases  were  brother  and  sister,  which  lent  support  to  his  theory 
that  the  disease  was  infectious.  Two  further  reports  were  due  to 
the  influence  of  Strumpell's  theory.  Briegleb  in  1890  published 
live  cases  which  occurred  close  together  near  Jena  within  a  period 
of  four  weeks.  Briegleb  published  these  cases  "  because  they  seem 
to  support  Strumpell's  theory,  that  a  disease  which  makes  its 
appearance  in  several  places  in  the  same  neighbourhood  and  at  the 
same  time  is  probably  caused  by  some  organized  morbid  agent." 
The  paper  by  Pleuss  is  very  similar;  in  1897  he  observed  four  cases 
in  the  neighbourhood  of  Kiel  within  three  months.  Hoffmann  in 
1904  observed  a  small  familial  group  of  cases  in  Dusseldorf.  A 
brother  and  sister  became  ill  on  the  same  day;  the  six-year-old  boy 
suffered  from  a  cerebral  hemiplegia,  the  four-year-old  sister  from 
spinal  paralysis.  Up  to  this  time  only  small  groups  of  cases  had 
occurred  in  Germany. 

But  matters  seemed  to  be  becoming  serious  when  Auerbach 
reported  no  fewer  than  fifteen  cases  in  the  months  May  to  Decem- 
ber, 1898,  in  Frankfurt  alone.  The  number  was  large  when  one 
considers  that  from  1892  to  1897  Auerbach  had  met  with  only  eleven 
cases.  The  groups  of  cases  reported  in  1908  were  larger,  one 
occurred  near  Heidelberg  (thirty-six  cases — Hoffmann),  one  near 
Hamburg  (twenty-two  cases — Nonne).  These  small  epidemics 
proved  to  be  the  forerunners  of  the  great  epidemic  of  1909  in 
Germany.  This  mainly  affected  Westphalia  and  Rheinland,  where 
certainly  700  cases  occurred.  The  epidemic  Avas  studied  by  many 
authors  (P.  Krause,  Meinicke,  Grober,  Reckzeh,  Wollenweber, 
Gasters,  Lasch,  Yieten).  It  then  passed  on  to  Hesse-Xassau, 
where  Ed.  Miiller  saw  130  cases,  and  used  them  for  his  clinical 
and  epidemiological  studies.  Thirty-four  cases  in  Hanover  (Eichel- 
berg)  followed,  about  fifty  cases  in  Schleswig  (O.  Forster),  and 
fifty-one  cases  in  Pomerania  (PieperJ.  At  least  1,000  cases 
occurred  in  Germany  during  1909.  It  appears  from  the  proceedings 
of  the  medical  societies  of  Berlin  that  further  groups  of  cases 
occurred  near  that  city  towards  the  end  of  1910.  The  progress  of 
the  epidemics  was  similar  to  that  in  Scandinavia,  at  first  only  small 
groups  of  cases,  then  small  epidemics,  and  finally  a  large  epidemic. 

Austria. — In  1898,  the  first  year  in  which  infantile  paralysis  was 
met  with  in  Germany  in  a  somewhat  epidemic  form.  Zappert  and 
Neurath  reported  on  groups  of  cases,  which  "  almost  constituted  an 
epidemic,"  in  the  neighbourhood  of  Vienna.  Forty-two  cases  were 
seen  during  the  summer  of  1898,  chiefly  in  August  and  September, 
while  only  129  instances  of  the  disease  had  been  met  with  during 
the   preceding   ten  years.        During   September  there   were   twelve 


EPIDEMIOLOGY  139 

cases,  a  figure  larger  than  the  average  yearly  number  for  the  ten 
years  before.  In  Austria  also  this  was  only  a  warning  of  what  was 
to  follow.  In  1908  there  was  an  epidemic  of  about  300  cases  in 
Vienna  and  Lower  Austria,  which  was  investigated  by  Zappert, 
Xenrath,  Frankl-Hochwart,  Locker,  Lindner  and  Alally.  and  many 
others.  The  epidemic  began  in  July,  and  reached  its  greatest 
height  in  September  and  October.  It  is  of  particular  historical 
interest,  because  it  was  the  occasion  on  which  Landsteiner  and 
Popper  successfully  transmitted  the  disease  to  monkeys.  In  1909 
the  epidemic  passed  on  to  Upper  Austria  and  the  Steiermark ; 
according  to  Furntratt  and  Potpeschnigg,  at  least  600  cases 
occurred.  Karnten  was  also  affected.  Potpeschnigg  made  the 
interesting  observation  that  the  large  epidemic  was  preceded  by 
several  small  ones  during  1906  and  1907.  In  Austria,  as  in  the 
other  countries,  the  same  warning  is  given  before  the  occurrence 
of  a  great  epidemic. 

Holland  and  Switzerland. — The  other  European  countries  have 
not  suffered  from  widespread  epidemics.  Groups  of  cases  have 
occurred  in  1906  and  in  1909  in  Holland,  but  no  epidemic.  During" 
1909  there  were  twenty-four  cases  in  Leyden,  and  fourteen  cases 
in  Warnsweld  and  Zutphen.  During  1910  cases  occurring  in  groups 
were  observed  in  Switzerland  by  Eichhorst  and  Hagenbach. 

England. — There  are  few  reports  from  England.  The  experi- 
ence of  Pasteur  in  1896  was  remarkable.  Seven  children  in  one 
family  became  ill  within  ten  days:  some  suffered  from  the  cerebral, 
some  from  the  spinal  form;  the  others  had  only  indefinite  feverish 
symptoms,  and  belonged  to  what  we  should  call  now  the  abortive 
type.  In  1897  Buzzard  observed  four  cases  in  London,  two  of 
which  were  brother  and  sister,  while  two  lived  in  adjacent  streets. 
Batten  saw  nine  cases  within  six  weeks  during  July  and  August, 
1902.  In  the  same  year  Mitchell  Stevens  made  a  similar  observation 
in  Cardiff.  In  1909  Treves  reported  a  small  epidemic  in  Upminster, 
and  Parker  collected  thirty-seven  cases  in  Bristol.  During  1910 
outbreaks  occurred  in  Carlisle  (thirty-four  cases — Beard),  Edinburgh 
(sixty-two  cases — Low),  Tillycoultry  (five  cases — Currie  and  Bram- 
well).  Barrow  (thirty-seven  cases — Garrow),  Maryport  (thirteen 
cases — Garrow),  and  South  Shields  (five  cases — Mostyn).  In 
191 1  the  number  of  small  epidemics  was  larger.  The  disease 
appeared  in  epidemic  form  in  Huntingdonshire,  Hampshire,  Stow- 
market,  Derbyshire,  Devon.  Cornwall  and  Dorset.  In  Devon 
and  Cornwall  no  less  than  224  cases  occurred  within  the  year 
(Reece).  Thus  in  England  the  same  phenomenon  is  seen  as  in 
other  countries.  The  small  epidemics  have  become  more  frequent 
and  involve  an  increasing  number  of  cases,  but  so  far  we  have  been 
spared  from  a  large  epidemic.  The  disease  was  made  compulsorily 
notifiable  in  London  in  September,  191 1,  and  in  some  provincial 
centres  since  then. 

France. — The  French  observations  are  not  without  interest  as 
they  are  analogous  in  many  respects  to  those  made  in  Scandinavia, 


140  EPIDEMIC   INFANTILE   PARALYSIS 

Germany,  and  Austria.  Cordier  reported  thirteen  cases  in  1888; 
they  were  collected  after  the  epidemic  in  Sainte-Foye  d'Argentiere, 
a  villag'e  with  1,400  inhabitants  near  Lyons;  there  were  four  fatal 
cases.  Cordiers  observations  make  it  probable  that  in  two  cases 
infection  could  be  traced  to  visits  made  to  patients  already  ill.  The 
cases  occurred  largely  in  adjacent  houses.  It  was  at  this  time  that 
the  contagiousness  of  the  disease  was  indicated.  In  1893  Andre 
saw  four  cases  near  to  Saint-Girons,  and  several  cases  in  Toulouse 
in  1895,  in  which  there  was  probable  infection  from  neighbours.  In 
the  same  year  Beclere  received  a  reliable  report  of  a  dozen  cases 
which  occurred  within  three  months  in  one  village.  The  same 
author  observed  the  disease  in  brother  and  sister  in  1898;  Guinon 
and  Rist  the  same  in  1903.  In  the  year  1909  there  was  a  definite 
epidemic  of  the  disease  in  Paris  and  its  surroundings;  Netter  states 
that  at  least  one  hundred  cases  occurred. 

Spain. — Only  small  epidemics  have  occurred  in  Southern 
Europe.  Roset  reported  a  small  epidemic  of  eight  cases  from  the 
neighbourhood  of  Vails  in  1896;  curiously  enough  five  cases  were 
hemiplegic  in  type. 

Italy. — There  are  many  reports  from  Italy,  but  they  all  concern 
groups  of  cases  or  quite  small  epidemics  (1895,  thirteen  cases  from 
the  surroundings  of  Padua,  observed  by  Cerevesato ;  in  the  same 
year  seven  cases  in  fifteen  days  in  Montespertoli  near  Florence, 
reported  by  Pieraccini).  In  1895,  Buccelli  saw  seventeen  cases  in 
Genoa,  which  all  occurred  in  the  same'  part  of  the  town,  several  in 
one  house  and  in  one  family.  Further  observations  are  those  of 
Fabris  (twenty-two  cases  in  the  years  1897,  1898  in  Conegliano), 
Simonini  (twenty  cases  in  September  and  October  in  Vicence),  and 
Lorenzelli  (twenty-six  in  1901  in  Parma). 

Russia. — There  is  one  communication  by  Jogichess  that 
grouped  cases  of  infantile  paralysis  occurred  in  St.  Petersburg  in 
the  years  1909  and  1910. 

North  America. — Great  epidemics  have  occurred  in  North 
America,  but  they  were  preceded  by  warning  outbreaks  in  the  shape 
of  groups  of  cases  and  small  endemics.  Thirty-eight  cases  were 
observed  in  Massachusetts  in  1892.  Caverley  and  Macphail 
reported  an  epidemic  of  126  cases  from  Vermont  in  1894,  which 
they  diagnosed  incorrectly  as  cerebrospinal  meningitis.  In  1896 
there  were  groups  of  cases  in  Alabama  and  Maine.  In  1897  H.  L. 
Taylor  observed  twelve  cases  in  a  small  district  of  New  York;  in 
1898  M.  Taylor  saw  four  cases,  two  of  these  were  brother  and  sister 
and  one  a  cousin  of  the  same.  In  the  same  year  Newmark  and 
Packard  observed  the  disease  in  families,  in  1899  Chapin  saw  seven 
cases  in  Poughkeepsie,  and  Mackenzie  seventeen  cases  in  Dutchess 
County,  in  1900  Painter  thirty-eight  cases  in  Boston,  and 
Bondurand  and  Woods  fifteen  cases  in  Alabama.  During  1901, 
fifty-five  cases  were  reported  from  San  Francisco;  in  1906  there  were 
large  groups  of  cases  of  infantile  paralysis  in  New  York  (Collins 
and  Romeiser). 


EPIDEMIOLOGY  141 

The  large  American  epidemics  began  in  1907.  In  New  York 
2,500  cases  occurred  (Collins,  Gibney,  Wallace,  Romeiser,  Koplik, 
Starr,  Berg,  Clowe,  and  others),  in  Massachusetts  there  were  234 
cases,  and  the  disease  spread  to  New  Jersey  and  Connecticut.  There 
was  a  small  epidemic  of  136  cases  (Lovett  and  Emerson)  in  Massa- 
chusetts in  1908,  also  in  Pennsylvania,  Iowa,  Wisconsin,  Michigan, 
and  Minnesota.  The  Nebraskan  epidemic  occurred  in  1909,  and 
during  these  three  years  (1907-1909)  the  number  of  children  affected 
had  risen  to  the  considerable  total  of  20,000. 

Flexner  says  that  few  of  the  States  have  been  spared;  the 
Southern  States  appear  to  be  free,  but  this  is  probably  due  to  faulty 
reports.  Flexner  further  points  out  that  the  epidemic  began  in  the 
States  on  the  east  coast,  which  receive  many  emigrants  from 
Scandinavia. 

Cuba. — Lebdreo  and  Recio  reported  an  epidemic  in  1909. 

South  America  appears  to  remain  free  from  the  disease. 

Australia. — Small  epidemics  have  been  reported  here  and  there. 
In  1895,  fourteen  cases  in  Port  Lincoln  (Alston);  in  1904,  chiefly 
during  March  and  April,  thirty-four  cases  in  Sydney  and  Brisbane 
(Wade);  in  1908,  135  cases  in  Melbourne  (Stevens). 

The  Origin  of  the  large  Epidemics. — The  preceding  facts  lead 
to  the  conclusion  that  it  is  the  northern  countries,  particularly 
Scandinavia  and  North  America,  which  are  most  attacked  by  the 
disease.  Large  epidemics  occurred  first  in  Scandinavia.  The 
occurrence  of  small  epidemics  shows  that  southern  countries  are 
by  no  means  immune  to  this  disastrous  scourge.  It  is,  perhaps, 
only  a  question  of  time  before  they  are  afflicted  by  a  great  epidemic. 

We  see  that  all  large  epidemics  are  preceded  by  warning  out- 
breaks in  the  shape  of  small  groups  of  cases.  It  is  doubtful  there- 
fore whether  the  view  that  Flexner  seems  to  take  is  correct,  that 
the  outbreak  of  a  severe  epidemic  is  determined  by  the  importation 
of  the  disease  from  Scandinavia,  although  the  fact  that  the 
Scandinavian  epidemics  antedated  the  others  seems  to  give  some 
support  to  this  view.  But  since  the  so-called  sporadic  form  of  the 
disease  has  always  been  found  extensively  in  each  country  before 
the  outbreak  of  an  epidemic,  and  since  we  know  that  the  sporadic 
and  epidemic  forms  are  identical,  there  seems  to  be  no  conclusive 
proof  that  the  epidemics  in  Germany,  Austria,  and  North  America 
have  been  due  to  importation  of  the  virus  from  Scandinavia.  It  is 
most  remarkable  that  a  disease,  which  had  been  well  known  in  its 
sporadic  form  for  many  years,  should  attack  groups  of  cases  in 
1880  and  onwards,  and  should  appear  in  epidemic  form  first  in  1905. 
Any  attempt  to  explain  this  must  remain  more  of  less  a  hypothesis. 
Some  suggest  that  the  cause  of  the  disease  became  more  virulent, 
and  instance,  in  support  of  this  theory,  that  fatal  cases  are  more 
frequent  during  epidemics  and  adults  are  more  often  attacked  than 
by  sporadic  poliomyelitis.  It  is  probable  that  both  these  statements 
are  incorrect;  when  there  was  no  epidemic  the  cause  of  death  was 
not  diagnosed  as  due  to  poliomyelitis,  nor  was  the  disease  diagnosed 


142  EPIDEMIC   INFANTILE  PARALYSIS 

as  such  in  adults  before  the  works  of  Medin  and  Wickman  became 
well  known.  The  following  is  a  possible  explanation  of  the  sudden 
appearance  of  the  disease  in  epidemic  form;  owing"  to  a  particular 
chain  of  causes  a  group  of  children  becomes  affected,  and  the 
resultant  accumulation  of  infective  material  makes  a  wider  dis- 
tribution of  the  disease  possible.  But  there  still  remains  the  ques- 
tion why  it  is  only  in  the  last  few  years  that  these  unknown  factors 
have  caused  this  accumulation  of  the  virus.  Possibly,  the  great 
increase  in  the  network  of  railways  has  resulted  in  a  wider  distri- 
bution of  infective  material.  In  truth,  we  are  quite  ignorant  of 
the  causes  which  have  produced  this  result,  and  can  only  confess 
the  fact. 

II.— THE  EPIDEMIOLOGICAL 

CHARACTERISTICS  OF  THE  SEVERAL 

OUTBREAKS. 

Season. — In  almost  all  the  outbreaks  mentioned  above  we  find 
certain  definite  relations  between  the  outbreak  of  an  epidemic  and 
the  time  of  year.  The  disease  is  pre-eminently  one  of  the  summer 
and  autumn,  in  particular  of  the  late  summer  and  early  autumn. 
The  following  curve  made  by  Wickman  demonstrates  very  clearly 
the  great  increase  in  the  number  of  cases  which  occurred  during 
the  months  of  July  to  October,  1905,  in  Sweden  (fig.  50). 

The  highest  point  of  an  epidemic  may  be  somewhat  delayed. 
This  happened  with  our  own  cases  in  Hesse-Xassau  which  were 
observed  by  Ed.  Muller;  he  found  many  more  cases  during  October 
and  November  than  in  August  and  September  (fig.  51).  The  com- 
parative distribution  of  the  cases  in  the  Swedish  epidemic  observed 
by  Wickman  and  of  those  of  our  own  epidemic  in  Hesse-Xassau  has 
been  put  into  tabular  form  by  Ed.  Muller  (figs.  52  and  53). 

Muller  is  probably  correct  in  surmising  that  the  delay  in  reach- 
ing its  highest  point  which  was  seen  in  our  epidemic  was  due  to 
the  fact  that  the  contagion  passed  over  to  us  from  Westphalia  rather 
late  in  the  year. 

Wickman  mentions  that  the  maximum  in  an  epidemic  may  be 
reached  during  the  winter  months.  Such  an  epidemic  was  recorded 
in  the  north  of  Sweden.  The  onset  of  winter  does  not  guarantee 
that  an  epidemic  will  cease  in  some  cases.  Here  I  may  mention 
again  the  extraordinary  resistance  to  cold  shown  by  the  virus.  The 
Australian  epidemics  are  no  exception  to  the  rule  that  the  disease 
occurs  during  the  summer  months,  because  March  and  April  in 
Australia  correspond  to  our  summer. 

Age,  Sex,  Predisposition.— Reports  from  the  different 
epidemics  agree  as  regards  the  usual  ages  at  which  patients  are 
attacked  by  the  disease.  Children  are  most  affected,  although  the 
epidemics  show  very  clearly  that  adults  are  attacked  more  often 
than  was  formerly  supposed.     The  percentage  rate  of  incidence  of 


EPIDEMIOLOGY 


143 


the   disease  cannot  be   expressed  more   clearly  than   by  the   curves 
constructed  by  Ed.  Miiller  (figs.  54-57)- 

Ninety-six  per  cent,  of  all  cases  occur  during  the  first  decade 
(fig.  54),  and  nine-tenths  of  these  children  had  not  readied  the  age 
of  five  years  (fig.  55).  More  than  three-quarters  of  the  cases 
occurred"  during  the  first  three  years  of  life,  of  these  most  in  the 
second  year  (fig.   56),  and  mainly  in  the  second  half  of  that  year 


Jan. 

Feb. 

Mar. 

April 

May 

June 

July 

Aug.  Sept. 

Oct. 

Nov. 

Dec. 

350 

-  ! 

1           1 

300 

550 
200 

— 1 — 

/            '        > 

150 

100 

to 

- 



• 

1 

■k 

Fig.  50. 

Monthly     number     of     cases     of     Heine-Medin 
disease  in   Sweden   (after  Wickman). 


50°/o 
40% 
30°/o 
20% 
lOO/o 
0°/o 


Aug. 

Sept.    Oct. 

Nov.     Dec 

- 

«V?a 

1 

" 

\«?» 

/                   \ 

/ 

\ 

~6% 

--"WMl 

k 

FIG. 


Percentage  of  fre- 
quency of  cases  in 
Hesse  -  Nassau  from 
August  to  December, 
1  909  (after       Ed. 

Miiller). 


Fig.  52. 

Distribution  of  Wickman;s  cases 
in  the  third  and  fourth  quarters 
(Swedish  epidemic,  1905).  (After 
Ed.  Miiller.) 


50°  0 
60% 

III  Q.  IV.  Q 

:  «•. 

-           / 

-         / 

60% 
40% 
S0% 
20% 
IOO/0 
0% 

-        / 

-      J 

-       \ 

-       \ 

-  1SV 

- 

Fig.  53- 

Distribution  of  cases  in  Hesse- 
Nassau  in  the  third  and  fourth 
quarters.     (After  Ed.   Miiller.) 


(fig.    57).     The   experience    of   other   investigators   at    other   places 
coincides  with  this. 

Males  are  somewhat  more  affected  than  females,  but  the  differ- 
ence is  not  large.     Most  observers  have  been  unable  to  detect  any 


144 


EPIDEMIC   INFANTILE   PARALYSIS 


indications  that  predisposition  plays  any  role  in  the  disease.  Strong 
and  healthy  children  are  affected  quite  as  often  and  as  severely  as 
weakly  children;  in  particular,  children  with  a  neuropathic  taint 
show  no  special  liability  to  the  disease. 

While  discussing  the  pathogenesis  of  the  disease  I  have  already 
touched  on  the  question :  Why  children  are  so  easily  and  frequently 
attacked. 


100% 
80% 
80% 
70% 
60% 
SOO/o 
40% 
30% 
20% 
lOO/o 
0% 


-1  D.  -2D.  -3D. 


|Z'»  Z 


»0% 

80% 
70% 
«0% 
60% 

(0"„ 
•0% 

ao% 

lOO/o 

-iY. 

-ioY 

-isY 

-20Y" 

-25Y 

-30Y. 

|«% 

" 

" 

, 

- 

- 

^U 

7% 

2% 

^0% 

Fig.  54- 

Percentage  distribution  of  the 
cases  among  the  first  three  decades 
of  life.      (After  Ed.   Muller.) 


FIG.    55- 

Percentage  distribution  of  cases 
in  the  first  six  5-yearly  periods  of 
life.      (After  Ed.   Muller.) 


-lY.   -2Y.  -3Y.  -4Y.  -5Y.  -6Y.  -?Y.  -8Y.  -9Y. -10Y. 


- 

A3 

?°o 

-  / 

\20 

_«% 

- 

Vr 

^ 

vs. 

J°o 

~~!2£. 

0'. 

iv. 

Fig.  56. 

Percentage  distribution  of  cases  in 
the  first  ten  years  of  life.  (After  Ed. 
Muller.) 


60% 
50% 
40O/o 
30% 
20% 
10  0/0 
0% 


•IM.  -12  M -18  M. -24  M. 


- 

50% 

- 

- 

- 

21,1- 

'       / 

-  / 

^•ttl 

Z'/. 

_  >a< 

% 

FIG.    57- 

Percentage  distribution  of 
cases  in  the  first  four  half  years 
of  life.      (After  Ed.  Muller.) 


Proof  Of  Contagiousness. — Now  that  a  living  micro-organism 
is  known  to  be  the  cause  of  Heine-Medin  disease,  the  question  arises 
as  to  how  infection  takes  place  and  what  are  the  sources  of 
contagion. 

The  first  observations  to  be  mentioned  are  those  which  relate 
to  the  occurrence  of  paralysis  in  certain  animals,  chiefly  in  dogs, 
fowls  and  rabbits,  at  the  same  time  as  epidemics  of  infantile 
paralysis  in  human  beings.  Such  a  coincidence  is  very  hypothetical, 
and   is  rendered    still   more   unlikely   by   the   number   of   epidemics 


EPIDEMIOLOGY  145 

which  have  been  observed  which  were  not  associated  with  any  such 
disease  in  animals.  The  evidence  obtained  from  experimental  work 
all  points  in  the  opposite  direction,  all  these  kinds  of  animals  being 
proved  to  be  not  susceptible  to  the  cause  of  Heine-Medin  disease  in 
man.  It  would  be  of  scientific  interest  to  determine  in  what  relation 
the  active  agent  of  Borna's  disease  in  horses  stands  towards  the 
virus  of  poliomyelitis  in  man,  because  of  the  extraordinary 
similarity,  not  to  say  identity,  of  the  microscopical  lesions  in  the 
two  cases. 

Since  it  is  exceedingly  doubtful  whether  the  disease  may 
be  transmitted  from  an  animal  to  man,  it  becomes  necessary  to 
determine  whether  infantile  paralysis  can  pass  from  man  to  man 
and  so  belong  to  the  contagious  variety  of  diseases.  In  this  con- 
nection the  older  observations  offer  a  certain  amount  of  evidence, 
e.g.,  Cordier's  statement  that  he  saw  the  disease  in  one  patient  who 
had  previously  visited  another.  The  occurrence  of  several  cases 
in  one  family  pointed  in  the  same  direction;  further,  Leegaard 
observed  that  an  epidemic  followed  the  lines  of  traffic. 

All  these  examples  were  only  significant,  and  until  1905  there 
was  no  clear  proof  of  the  contagiousness  of  the  disease;  up  to  that 
time  observers  were  inclined  to  take  rather  the  opposite  view,  e.g., 
Medin  thought  that  direct  infection  was  exceedingly  rare,  and 
Zappert  was  definitely  opposed  to  the  idea. 

The  exemplary  investigation  into  the  Swedish  Epidemic  of  1905 
by  Wick-man  turned  the  current  of  opinion  in  a  contrary  direction. 

Wickman  worked  under  particularly  favourable  conditions; 
owing  to  compulsory  notification  being  enforced  by  the  Govern- 
ment he  was  able  to  investigate  every  single  case.  Further,  the 
lonely  parishes  of  Sweden  with  their  isolated  farms  and  houses  made 
it  possible  to  trace  the  course  of  the  epidemic  under  very  simple 
conditions.  Wickman  did  not  shirk  the  labour  of  tracing  every 
case,  and  he  made  it  possible  to  obtain  a  clear  general  view  of  the 
individual  cases  by  the  use  of  maps.  Xo  one,  who  wishes  to 
gain  a  thorough  knowledge  of  the  epidemiology  of  the  disease,  can 
avoid  the  trouble  of  carefully  examining  the  studies  of  Wickman. 

We  shall  only  summarize  Wickman's  arguments,  by  which  he 
proved  that  Heine-Medin  disease  is  contagious,  i.e.,  communicable 
from  man  to  man. 

In  the  first  place,  in  the  Swedish  epidemic  it  was  possible  to 
prove  contact  between  the  individual  cases  almost  universally.  It 
is  true  that  contact  was  not  direct  in  every  case,  frequently  there 
were  intermediaries  who  remained  healthy.  Wickman  would  never 
have  been  able  to  establish  this  fact  if  he  had  not  known  of  the 
abortive  cases  from  his  clinical  studies  and  had  not  taken  them  into 
consideration.  When  this  is  not  done  it  happens  too  often,  as  I 
mentioned  in  the  first  chapter,  that  the  hasty  and  incorrect  conclu- 
sion is  reached  that  no  contact  has  occurred  between  the  cases. 
Wickman  made  a  careful  analysis  of  the  circumstances  accom- 
panying infection  in  almost  every  case,   1,031  in  all. 

10 


I46  EPIDEMIC  INFANTILE  PARALYSIS 

His  observations  in  the  little  parish  of  Traestena  have  become  specially 
celebrated,  because  they  form  a  classical  example  of  his  theory  that  the 
disease  is  contagious.  Out  of  500  inhabitants,  living  in  102  houses,  mostly 
isolated  from  one  another,  49  persons  (=  10  per  cent.)  became  ill,  26  of 
these  (=  5  per  cent.)  had  de'finite  paralysis.  The  source  of  infection  in  most 
cases  was  the  school ;  the  disease  was  carried  to  the  different  houses  by  the 
children,  some  of  whom  became  ill  themselves,  while  others  remained  well. 
Wickman  therefore  arrived  at  the  important  conclusion  that  the  disease 
could  spread  by  means  of  "  carriers,"  as  in  the  case  of  so  many  other  infec- 
tious diseases.  Where  it  was  not  possible  to  trace  the  infection  directly  to 
the  school,  it  could  be  proved  that  visits  had  taken  place  to  houses  which 
had  already  been  infected  from  the  school.  The  infection  spread  from  this 
parish  in  a  radial  manner,  in  the  same  way  as  was  observed  in  larger 
affected  areas. 

Even  when  it  was  not  possible  to  trace  the  spread  of  the 
epidemic  so  clearly  as  in  the  above  example,  yet  the  grouping  of 
the  cases  was  important;  in  many  instances  several  persons  in  one 
house  or  in  adjacent  houses  were  attacked.  Further,  the  connec- 
tion between  the  chief  roads  and  railways  and  the  spread  of  the 
disease  was  very  evident,  particularly  among  the  more  scattered 
cases. 

From  all  these  facts  Wickman  came  to  the  conclusion  that 
Heine-Medin  disease  behaves  exactly  like  other  contagious  diseases 
as  far  as  its  method  of  spread  is  concerned.  Wickman  explained 
also  why  this  had  not  been  recognized  before.  The  earlier  small 
epidemics  had  not  given  opportunities  for  such  observations,  and 
the  importance  of  abortive  cases  and  of  healthy  carriers  had  not 
been  recognized. 

Wickman  considers  that  indirect  transmission,  i.e.,  by  non- 
living objects,  is  a  great  rarity.  He  himself  only  met  with  one 
case  in  which  the  infection  was  carried  by  a  picture,  and  one  in 
which  the  milk  was  blamed.  These  observations  have  remained 
unique;  no  similar  examples  of  indirect  transmission  have  been 
reported. 

Confirmation  of  Wickman's  Statements. — Subsequent  epi 
-demies  provided  excellent  opportunities  of  testing  Wickman's 
conclusions.  In  our  epidemic  in  Hesse,  Mullef  succeeded  in 
tracing  very  clearly  the  track  of  the  epidemic,  because  the  number 
of  cases  was  not  very  great,  and  in  many  villages  only  one  case 
occurred.  A  tendency  to  grouping  of  the  cases  was  observed. 
As  in  Sweden,  it  was  abundantly  clear  that  the  infection  followed 
the  lines  of  the  railways  and  the  great  roads.  Miiller  was  able  to 
find  cases  in  which  the  infection  was  brought  by  healthy  carriers 
and  could  have  been  brought  in  no  other  way. 

A  particularly  instructive  example  was  provided  in  the  case  of  the  small 
epidemic  in  the  little  town  of  Frankenau.  The  midwife  of  the  town  had 
visitors  from  Westphalia  from  September  11  to  the  13th.  On  the  20th  one 
of  her  children  was  stricken  with  paralysis  and  two  others  suffered  from 
gastro-intestinal  symptoms.     Some  time  later  a  neighbour's  child,  who  had 


EPIDEMIOLOGY  147 

played  with  the  children  of  the  midwife  who  had  remained  unaffected, 
became  ill,  so  also  a  child  of  the  schoolmaster  (the  healthy  children  of  the 
midwife  attended  the  school);  finally,  the  child  of  a  workman  became  ill, 
who  had  been  in  the  same  schoolroom  with  the  midwife's  children.  The 
track  of  the  epidemic  was  therefore  as  follows  :  The  virus  was  brought  by 
healthy  carriers  from  Westphalia;  in  the  village  it  was  disseminated  by  the 
healthy  children  of  the  midwife. 

Direct  transmission  of  the  disease  by  the  patient  was  more  rare, 
a  fact  which  had  been  observed  by  Wickman.  Muller  found  the 
disease  less  among"  the  peasants  who  remained  on  their  land  than 
among  those  who  followed  a  trade,  particularly  those  that  came 
much  into  contact  with  the  rest  of  the  world  (inn-keepers,  coach- 
men, postmen,  and  railway  workers);  shoemakers  or  their  children 
were  curiously  often  affected,  a  fact  noticed  also  by  Eichelberg. 

Confirmation  of  Wickman' s  observations,  particularly  of  those 
with  reference  to  the  subject  of  the  healthy  carrier,  was  given  by 
the  reports  of  Krause  (Westphalia),  Leegaard  (Norway),  Xetter 
(France),  of  Locker,  Lindner  and  Mally  (Upper  Austria),  and  also 
of  Emerson,  Armstrong,  Jones,  Shidler,  and,  to  a  certain  extent, 
Lovett,  who  all  reported  American  epidemics. 

Zappert  is  very  reserved  in  his  opinion  on  the  contagiousness 
of  the  disease.  He  observed  grouping"  of  the  cases  in  Lower 
Austria;  in  Vienna  itself  the  disease  appeared  in  certain  quarters  of 
the  city  and  in  certain  groups  of  houses;  occasionally  he  saw  more 
than  one  case  in  the  same  family;  but  he  was  quite  unable  to  trace 
any  connection  between  the  different  cases.  It  must  be  remembered 
that  he  had  to  carry  out  his  research  in  a  large  capital  and  in  a  thickly 
populated  province. 

No  proofs  of  the  contagiousness  of  the  disease  could  be  obtained 
in  the  great  epidemic  in  New  York  in  1907,  nor  in  the  epidemic  in 
the  Steiermark  (Furntratt,  Potpeschnigg)  nor  in  Pomerania 
(Peiper).  Wickman  quite  rightly  emphasizes  the  fact  that  all  these 
■observers  were  unable  to  prove  any  other  method  of  transmission 
■of  the  disease. 

The  reasons  usually  brought  forward  against  the  theory  of 
•contagion  are  the  occurrence  of  completely  isolated  cases,  the 
observation  that  so  often  only  one  child  in  a  family  is  affected, 
the  absence  of  any  epidemics  in  hospitals,  and  the  occasional 
appearance  of  the  disease  among  the  "most  isolated"  people 
(prisoners!).  It  is,  however,  questionable  whether  these  isolated 
people  are  really  so  isolated  as  they  appear  to  be;  in  particular  it 
must  be  remembered  that  abortive  cases  may  have  occurred  in  the 
neighbourhood  and  that  contact  with  healthy  carriers  is  possible. 
Serum  diagnosis  may  throw  some  light  on  these  cases  (see  following 
■chapter). 

Wickman  justly  draws  the  comparison  between  Heine-Medin 
■disease  and  cerebrospinal  meningitis;  the  epidemiology  of  the  two 
diseases  has  many  points  in  common;  in  both,  children  are  chiefly 
affected,  adults  are  not  entirely  immune,  only  one  or,  at  most,  two 


I48  EPIDEMIC   INFANTILE   PARALYSIS 

children  in  a  family  are  affected,  the  disease  is  certainly  transmitted 
by  healthy  carriers,  "  sporadic  "  cases  occur,  and  finally,  no  com- 
pletely satisfactory  explanation  of  the  epidemic  occurrence  of  the 
diseases  has  ever  been  found.  Scarlet  fever  might  be  instanced  for 
comparison  on  many  points. 

No  sound  argument  has  been  brought  against  the  contagion 
theory  so  far. 

All  attempts  to  find  another  way  by  which  the  infection  travels 
have  failed,  such  as  transmission  by  drinking-water  (epidemics  in 
towns  with  a  faultless  water  supply),  by  fruit  (epidemics  at  a  time 
when  there  was  no  fruit),  by  cow's  milk  (children  at  the  breast  have 
contracted  the  disease,  see  Wickman's  exception  quoted  above), 
and  by  other  articles  of  food.  Transmission  by  insects  is  not  pro- 
bable because  of  the  occasional  epidemics  during  the  winter. 

Certain  observations  seem  to  support  the  idea  that  the  virus 
may  remain  in  a  house  (i.e.,  on  non-living  things)  and  thus  be 
transmitted.  That  the  virus  has  been  proved  experimentally  to 
remain  active  for  a  long  time  is  an  argument  in  favour  of  this  view, 
which  deserves   consideration. 

We  agree  with  Wickman  that  the  chief  method  of  transmission 
of  the  disease  is  the  direct  one,  from  human  being  to  human  being. 

It  is  very  difficult  to  say  how  infection  takes  place.  When 
discussing  the  pathogenesis  of  the  disease  we  arrived  at  the  con- 
clusion that  probably  the  lymphatic  tissues  of  the  mouth,  nose, 
throat,  and  alimentary  tract,  served  as  the  portal  of  entry  of  the 
virus.  Many  things  point  to  the  virus  remaining  for  a  long  time 
in  the  mucous  membrane  of  the  mouth  and  throat  of  infected 
individuals.  One  might  think  of  infection  by  the  saliva  in  speaking, 
coughing,  sneezing,  or  in  more  direct  contact.  Unfortunately 
there  is  as  yet  no  proof  that  the  virus  is  contained  in  the  saliva. 
I  have  given  monkeys  an  intracerebral  injection  of  saliva  filtered 
through  a  Berkefeld  filter  from  cases  of  poliomyelitis  and  have  not 
succeeded  in  producing  the  disease.  Considering  how  little  we 
really  know  about  the  pathogenesis  of  the  disease,  any  attempt  to 
explain  how  infection  occurs  under  the  conditions  of  an  epidemic 
must  be  fraught  with  almost  insuperable  difficulties. 

One  fact  may  be  accepted  as  practically  proved  by  Wickman — 
the  disease  is  contagious.  Xo  one  knows  how  infection  takes 
place,  whether  by  direct  contact,  by  the  breath,  by  virus  which  has 
adhered  to  non-living  objects,  clothes  and  shoes,  or  finally,  by 
some  animal  carrier  which  has  been  overlooked.  We  are  still  at 
the  beginning  of  this  question. 

There  are  tzi'o  mysteries  awaiting  an  explanation.  The  one  is- 
general  in  character,  the  question  hozu  the  great  epidemics  arise. 
The  other  is  particular,  how  does  infection  fake  place  in  each 
epidemic  ? 

[Kling,  Wernstedt,  and  Pettersson  bave  since  succeeded  in 
producing  the  disease  in  monkeys  by  using  saliva  and  intestinal 
contents.  Neustaedter  and  Thro  succeeded  in  using  dust  from  the 
sick-room  for  this  purpose. — Translator.] 


CHAPTER  VI. 

The  Fight  Against  the  Disease. 


I.— IMMUNITY     AND     IMMUNIZATION. 

Clinical  and  Epidemiological  Experience.— Before  attempting 
to  produce  artificial  immunity  to  an  infectious  disease,  it  is  necessary 
to  consider  whether  the  evidence  points  to  the  development  of  a 
natural  immunity  in  the  course  of  the  disease.  In  the  case  of 
Heine-Medin  disease  this  inquiry  leads  to  no  definite  conclusion  and 
is  beset  with  difficulties.  In  the  first  place,  we  have  only  recently 
become  acquainted  with  the  epidemic  form  of  the  disease ;  secondly, 
the  total  number  of  cases  is,  fortunately,  relatively  small,  and  they 
occur  within  narrow  limits  of  ag'e.  Even  though  many  children 
survive  one  epidemic,  by  the  time  that  another  occurs  these  patients 
have  attained  an  age  in  which  infection  is  rarely  found.  It  is  con- 
sequently very  difficult  to  prove  by  figures  that  one  attack  of  Heine- 
Medin  disease  protects  against  a  second  attack. 

However,  it  is  worth  placing'  on  record  that  observers  who 
have  paid  special  attention  to  this  point  and  who  have  had  the 
opportunity  of  observing  large  epidemics,  have  never  seen  the 
disease  attack  the  same  child  twice  (Wickman,  Ed.  Miiller,  Stiefler). 
Harbitz  and  Scheel  observed  the  great  Norwegian  epidemic,  and 
state  that  "  it  seems  proved  beyond  doubt  that  when  a  district  has 
been  visited  by  the  disease  in  one  year,  it  remains  free  during  the 
following  years."  Zappert  came  to  the  same  conclusion  in  the 
course  of  his  extensive  studies.  In  1898  there  was  an  epidemic  in 
Vienna,  and  in  the  following  year  the  number  of  cases  was  much 
below  the  average;  this  corresponds  also  with  our  experience  with 
regard  to  other  infectious  diseases  :  the  number  of  cases  in  the  years 
following  an  epidemic  is  always  remarkably  small. 

There  are  a  few  records  which  indicate  that  the  same  individual 
may  suffer  twice  from  the  disease.  Eshner  saw  a  patient  who  had 
the  first  attack  at  the  age  of  three  and  the  second  at  fourteen.  The 
exact  nature  of  the  second  illness  is,  however,  not  quite  clear;  it  is 
not  impossible,  though  improbable,  that  it  was  really  a  traumatic 
neuritis.  Eckert  reported  another  case,  unfortunately  giving  very 
meagre    details:        "  H.     Sch.    was    attacked    by    poliomyelitis    in 


150  EPIDEMIC  INFANTILE  PARALYSIS 

September,  1903.  Tenotomy  and  a  mechanical  support  were  neces- 
sary for  the  left  leg-,  which  was  paralysed.  At  the  beginning  of  April, 
1909,  he  suffered  from  a  second  attack,  in  which  the  right  leg  was 
paralysed."  Unfortunately  I  have  been  unable  to  see  the  original 
paper  by  Sterne,  quoted  by  Netter  and  Levaditi,  in  which  a  large 
number  of  cases  were  reported  in  adults,  who  had  suffered  from 
poliomyelitis  during  childhood.  In  these  cases  the  second  attack 
followed  9.   17,  19,  23,  and  54  years  after  the  first. 

It  is  quite  possible  that  if  immunity  be  established  it  does  not 
last  throughout  a  lifetime;  Sterne's  results  might  be  explained  on 
this  assumption.  Further,  it  must  be  remembered  that  increase 
of  paralysis  does  not  always  mean  a  second  attack  of  the  disease; 
a  spinal  cord  which  has  once  been  damaged  is  particularly  liable 
to  further  damage  of  a  non-specific  kind,  with  destruction  of  those 
elements  which  had  remained  capable  of  functioning.  But  even 
although  isolated  cases  of  reinfection  do  occur,  that  does  not  do 
away  with  the  possibility  that  survival  of  one  attack  leaves  behind 
it  a  specific  protection  against  another.  Even  in  the  case  of 
diseases,  such  as  small-pox,  in  which  this  occurs  to  a  very  marked 
degree,  occasional  exceptions  to  the  law  of  immunity  are  met  with. 
Biological  laws  are  not  mathematical  in  their  application. 

Relapses,  which  are  very  rare,  constitute  no  proof  that 
immunity  is  not  conferred  by  an  attack  of  the  disease.  Medin  and 
Neurath  both  observed  relapses.  Wickman  found  them  exceedingly 
rarely,  and  Ed.  Miiller  not  at  all.  I  once  saw  a  relapse  in  a  case 
of  experimental  poliomyelitis  (see  p.  59).  Under  these  circum- 
stances they  appear  to  be  extremely  rare,  and  I  believe  that  the  two 
cases  described  by  Levaditi  and  myself  are  the  only  instances 
known. 

All  these  observations  fail  to  prove  that  immunity  is  not  con- 
ferred, and  yet  it  is  very  difficult  to  obtain  exact  proof  of  the 
opposite,  if  one  ignores  the  general  impression  obtained  from  the 
study  of  epidemics.  In  the  case  of  monkeys,  which  behave  towards 
the  virus  in  other  respects  just  like  human  beings,  it  is  quite  certain 
that  immunity  is  present.  This  makes  it  probable  that  in  man  one 
attack  produces  immunity  for  a  longer  or  shorter  period  against  a 
second  attack. 

The  existence  of  such  immunity  may  explain  some  of  the 
observations  made  during  epidemics.  Wickman  was  struck  by  the 
small  incidence  rate  of  the  disease.  In  the  district  which  was 
most  severely  affected  only  5  per  cent,  of  the  inhabitants  became 
paralysed;  the  inclusion  of  all  abortive  cases  only  brought  the 
figure  up  to  10  per  cent.  Now,  Wickman's  observations  offer 
convincing  proof  that  the  virus  may  be  transmitted  by  healthy 
carriers;  we  know  also,  from  our  experience  with  typhoid  fever, 
cholera,  and  other  diseases,  that  these  clinically  healthy  carriers 
have  suffered  from  the  infection  in  some  way  or  another,  because 
specific  products  of  reaction  to  the  virus  can  be  found  in  their 
blood-serum.     It  seems  to  me  worth  considering  whether  we  shall 


THE    FIGHT     AGAINST    THE     DISEASE  151 

not  eventually  find  specific  antibodies  in  the  serum  of  a  large 
number  of  apparently  healthy  people  during  an  epidemic.  Such  a 
discovery  would  be  of  the  greatest  importance  epidemiologically 
and,  merely  as  a  working  hypothesis,  such  a  consideration  will  be 
of  value  to  future  investigators. 

Attempts  to  Reinfect  Monkeys. — Apart  from  all  epidemi 
ological  considerations  it  would  have  been  natural  to  make  investi- 
gations into  the  question  of  immunity  in  experimental  poliomyelitis. 
The  existence  of  a  successful  method  of  protective  inoculation  in 
the  case  of  the  analogous  disease  of  rabies,  although  the  epidemi- 
ology of  that  disease  offered  no  evidence  of  the  occurrence  of 
immunity,  would  in  itself  have  stimulated  us  to  make  the  experi- 
ment. The  following  is  a  series  of  experiments  in  which  monkeys 
which  had  survived  the  first  infection  were  given  a  second  injection 
of  the  virus. 

Experiment  1. — On  December  28,   igog,  the  following  monkeys  received 
an  intracerebral  injection  of  '5  c.c.  of  an  emulsion  of  virus  No.   11. 

(a)   Control  monkey  No.   16  {Macacus  rliesus). 

December  2Q-January  2. — Well. 

January  3. — In  the  evening  rather  tired,  looks  cross. 

January    4. — Severe   flaccid    palsy    of   both    arms  and   the    neck;    slight 
weakness  in  the  hind  limbs. 

January  5. — Lies  on  the  floor,  apparently  completely  paralysed.      Death 
at  noon.     Microscopical  appearances  typical. 

(b)  Monkey  No.  6  (Macacus  rhesus)  received  an  intracerebral  injection  of 
'8  c.c.  of  virus  of  Case  3,  passed  through  Berkefeld  filter,  on  December  2 
and  4.  Remained  perfectly  well.  Interval  between  the  two  infections 
twenty-four  to  twenty-six  days. 

Course  of  the  infection  on  December  28  :  — 

December  29-January  7. — No  symptoms. 

January  8. — Spares  the  right  hind  limb. 

January  9. — Paresis  of  right  hind  limb  more  noticeable. 

January   10. — Paresis  scarcely  to  be   seen. 

January  11. — Still  slight  paresis. 

January    12    et    seq. — Well.      The    monkey    lived    until   June    15,    1910; 
occasionally  a  trace  of  weakness  was  noticed  in  the  right  hind  limb. 


Experiment  2. — The  following  monkeys  received  an  intracerebral 
injection  of  "5  c.c.  of  virus  No.  12  on  January  3,  1910  :  — 

(a)  Control  monkey  No.    17   (Macacus  rhesus). 
January  4-15. — Well. 

January   16. — Sad  and  cross. 

January   17. — Flaccid  paralysis  of  both  hind  limbs. 

January  18. — Lies  on  the  floor  of  the  cage  with  all  limbs  apparently 
paralysed.      Death  in  the  evening. 

Microscopical  appearances  typical. 

(b)  Monkey  No.  8  (Cerco-pithecus  ruber)  received  '4  c.c.  of  virus  No.  3 
(intracerebral  injection)  on  December  4,  1909;  afterwards  suffered  from  the 
abortive  type  of  the  disease  (see  p.  38). 

Interval  between  the  injections,  thirty  days. 

Result  of  injection  January  3. — Remained  quite  well. 


152  EPIDEMIC    INFANTILE   PARALYSIS 

Experiment  3. — The  following  monkeys  received  an  intracerebral 
injection  of  an  emulsion  of  virus  Xo.    11   on  January  6,   1910  :  — 

(a)  Control  monkey  (Mangabey)  received  '2  c.c.  January  7-17.  Xo 
symptoms. 

January  iS. — In  the  afternoon,  definite  flaccid  paresis  of  both  hind  limbs. 

January  19. — Paresis  more  marked.      Slight  paresis  of  the  arms. 

January  20. — Total  flaccid  paralysis  of  both  hind  limbs:  definite  slight 
paresis  of  the  arms. 

January  21-23. — Gradual  increase  of  paralysis. 

January  24. — Total  paralysis  of  all  limbs.  Death  in  the  afternoon. 
Microscopical  appearances  typical  and  extensive. 

(b)  Monkey  No.  9  (Mangabey)  received  a  subcutaneous  injection  of  1  c.c. 
of  an  emulsion  of  the  virus  of  Case  3  on  December  4,  1909.  and  remained 
well. 

Interval  between  the  two  inoculations  thirty-three  days. 
Result    of    re-infection    ('2    c.c.    intracerebral). — Remained    permanently 
well. 

(c)  Monkev  Xo.  10  (Mafigabey)  received  an  intraneural  injection  of  "2 
c.c.  of  the  virus  from  Case  3  on  December  4,  1909,  and  remained  well. 

Interval  between  the  inoculations,  thirty-three  days. 

Result  of  reinfection  ('5  c.c.  intracerebral,  i.e.,  two  and  a  half  times 
the  dose  given  to  the  control)  :  — 

January  16-19. — Trace  of  paresis  of  left  fore  limb. 

Januarv  20  et  seq. — Quite  well.  General  condition  remained  normal 
throughout. 


Experiment  4. — The  following  monkeys  received  intracerebral  injections 
of  '35  c.c.  of  virus  Xo.  12  on  February  7,  1910. 

(a)  Control  monkey  No.  29  (Macacus  rhesus). 
February  S-14. — Well. 

February   15. — Paralysed. 

February  22. — Death.      (For  details,  see  p.  47.) 

(b)  Monkey  Xo.  9  [Mangabey).  For  previous  inoculation  see  Experi- 
ment 3.  Period  between  the  second  and  third  infection  on  February  7  was 
thirty-two  days.     Result  of  last  infection — Remained  permanently  well. 

(c)  Monkey  Xo.  10  (Mangabey).  For  previous  infection,  see  Experi- 
ment 3.  Period  between  that  infection  and  the  one  on  February  7  was 
thirty-two  days.      Result — remained  well. 

(d)  Monkey  Xo.  6  (Macacus  rhesus).  For  previous  infection  see  Experi- 
ment 1.  Interval  between  inoculations,  forty-one  days.  Result  of  last 
infection — Remained  well. 


Experiment  5. — The  following  monkeys  received  an  intracerebral  injec- 
tion of  '6  c.c.  of  virus  Xo.  11  on  March  15,  1910  :  — 

(a)  Control  monkey  Xo.  41   (Macacus  cynomolgus). 
March  16-25. — Remained  well. 

March  26. — Paresis  of  the  legs. 

March  27. — Paresis  more  marked. 

April  1  et  seq. — Gradual  improvement   (for  details,  .see  p.   59).' 

(b)  Monkey  Xo.  32  (Macacus  rhesus)  received  an  injection,  causing  a 
paralysis  which  gradually  improved,  on  February  7  \cf.  p.  58).  Interval 
between  first  and  second  inoculation,  thirty-six  days. 

Result  of  infection  on  March  15. — Remained  permanently  well. 


THE    FIGHT     AGAINST     THE     DISEASE  1 53 

Experiment  6. — The  following  monkeys  received  an  intracerebral  injec- 
tion of  '6  c.c.  of  virus  Xo.   n  on  July  13,  1910  :  — 

(a)  Control  monkey  Xo.   102  (Macacus  rhesus). 
July   14-24. — Well. 

July  25. — Flaccid  paresis  of  hind  limbs  and  weakness  of  the  trunk. 
In  the  evening  paralysis  of  the  hind  limbs  and  of  the  left  fore  limb ; 
right-sided  facial  palsy. 

July  26. — Found  dead.     Microscopical  appearances  typical. 

(b)  Monkey  No.  59  (Macacus  rhesus)  received  an  injection  on  June  13, 
1910,  which  caused  paralysis  which  improved.  Interval  between  the  infec- 
tions, thirty  days. 

Result  of  reinfection. — Remained  permanently  well. 

In  six  different  series  of  experiments  nine  reinfected  monkeys 
proved  to  be  immune  to  an  infection  which  caused  severe  paralysis 
in  the  control  monkeys  and,  with  one  exception,  caused  death. 
The  interval  between  infection  and  reinfection  varied  from  twenty- 
four  to  forty-one  days  in  my  experiments. 

The  work  of  other  experimenters  provides  further  proof  that 
a  monkey  that  has  survived  infection  with  poliomyelitis  is  immune. 
Landsteiner  and  Levaditi  reported  the  following-  experiment  on 
January  3,  1910 : — 

Three  monkeys  (Macacus  rhesus,  and  Macacus  cynomolgus),  of  which 
two  had  been  paralysed  for  twelve  days  and  the  third  for  twenty-five  days, 
together  with  a  control  monkey  (Macacus  cyuouwlgus),  were  reinfected. 
The  control  became  paralysed  in  five  days,  and  died  on  the  sixth  day.  The 
three   reinfected  monkeys  remained   well. 

The  experiment  shows  that  immunity  is  present  twenty-one 
days  after  the  first  infection  and  twelve  days  after  the  appearance 
of  paralysis. 

Flexner  and  Lewis  were  the  first  to  report  a  reinfection  experi- 
ment on  January  1,  1910:  — 

Monkey  45,  paralysed  as  a  result  of  an  intracerebral  infection  on 
November  6,  1909,  was  reinfected,  together  with  two  control  monkeys,  on 
November  30,  igog.  The  latter  became  typically  paralysed,  the  reinfected 
monkey  remained  well. 

In  their  summary  of  later  date  Flexner  and  Lewis  report  that 
they  had  found  monkeys  to  be  immune  from  eight  days  to  two 
months  after  the  onset  of  paralysis. 

The  experience  of  Leiner  and  v.  Wiesner  was  similar.  They 
published  no  less  than  twelve  separate  experiments  with  a  positive 
result;  reinfection  was  performed  2,  7,  9,  25,  31,  41,  52,  55,  60,  66, 
87  and  99  days  after  the  occurrence  of  paralysis.  They  have  per- 
formed the  service  of  showing  that  immunity  is  present  as  early  as 
two  days  and  at  least  as  late  as  ninety-nine  days  after  the  appear- 
ance of  paralysis. 

The  summation  of  all  these  similar  results  leaves  no  doubt  that 
the  survival  of  an  attack  of  poliomyelitis  which  is  accompanied  by 
paralysis    confers    immunity    upon    monkeys.      The    condition    laid 


154  EPIDEMIC   INFANTILE   PARALYSIS 

down  by  Krause  and  Meinicke  is  not  necessary,  viz.,  that  long- 
series  of  experiments  in  more  suitable  animals  are  required  before 
the  fact  of  immunity  can  be  conclusively  proved.  There  is  also  no 
doubt  that  Krause  and  Meinicke  are  wrong  in  believing  that  increase 
in  the  age  of  the  monkeys  can  be  the  cause  of  the  immunity  in  the 
experiments  detailed  above. 

Immunity  after  an  attack  which  has  caused  paralysis  seems  to 
be  the  rule  in  monkeys.  The  only  experiment  with  an  opposite 
result  is  one  quoted  by  Leiner  and  v.  Wiesner  :  Monkey  No.  172, 
infected  on  February  11.  1910,  was  paralysed  on  February  23. 
It  was  reinfected  on  March  12,  and  became  ill  and  more  paralysed 
on  March  30.  (The  control  became  paralysed  on  March  17.)  In 
this  case  the  shortness  of  the  incubation  period  in  the  control 
renders  it  probable  that  the  infection  was  very  severe,  and  this 
single  case  does  not  disprove  the  rule  of  immunity.  After  all,  every 
immunity  is  relative. 

It  is  more  difficult  to  determine  whether  an  infection  which 
does  not  cause  paralysis  confers  immunity.  I  have  the  impression 
that  an  unsuccessful  inoculation  increases  the  resistance  of  the 
animal  (cf.  Experiment  3  above);  but  I  have  no  doubt  that  the 
immunity  thus  conferred  is  neither  so  certain  nor  so  powerful  as 
that  which  follows  definite  paralysis.  The  following  experiments 
show  that  reinfection  may  be  successful  when  the  first  infection  has 
had  no  result :  — ■ 

Experiment  7. — The  following  monkeys,  on  December  14,  IQ09,  received 
an  intraperitoneal  injection  (3  c.c.)  and  an  intracerebral  injection  ('5  c.c.) 
of  a  20  per  cent,  emulsion  of  virus  Xo.   11. 

(a)  Control    monkey    No.     13     (Macacus    rhesus). 
December  15-25. — Well. 

December  26. — Paresis  of  the  hind  limbs. 

December  27. — Marked  paralysis  of  the  hind  limbs,  commencing  para- 
lysis of  the  fore  limbs. 

December  28-January  2,   1910. — Slight  improvement. 

January  3. — Paralysis  more  marked. 

January  4. — Total  paralysis. 

January  5. — Found  dead.      Microscopical   appearances  typical. 

(b)  Monkey  No.  4  (Macacus  rhesus)  received,  on  November  27,  190Q, 
an  intracerebral  injection  of  an  emulsion  of  virus  from  Case  2  (see  p.  37), 
and  suffered  subsequently  from  a  doubtful  (  ?  abortive)  poliomyelitis  from 
the  fifth  to  the  seventh  day  after  the  infection.  Interval  between  the  infec- 
tions, seventeen  days. 

Result  of  reinfection  on  December  14. — 
December  15-22. — No  symptoms. 
December  23. — Definite  paresis  of  all  limbs. 
December  24. — Total  paralysis  of  all  limbs;  death. 
Microscopical  appearances  typical. 


Experiment    8.— -The    following    monkeys    were    given    an    intracerebral 
injection  of  '5  c.c.  of  virus  No.  6  on  December  17,   1900. 
(a)   Control  monkey  No.   14  (Macacus  rhesus). 


THE    FIGHT     AGAINST    THE     DISEASE  155 

December  18-25. — Well. 

December  26. — Paralysed. 

December  30. — Death   (for  details,  see  p.   48). 

(b)  Monkey  No.  5  {Macacus  rhesus)  was  given  an  intracerebral  injection 
of  virus  No.  6  on  December  1,  1909,  and  remained  well.  Interval  between 
the  two  infections,  sixteen  days. 

Results  of  the  reinfection  :— - 

December    18-23. — No   symptoms. 

December  24. — Paresis  of  the  right  hind  limb. 

December  25. — Paralysis  of  all  limbs. 

December  28. — Death. 

I  believed  at  first  that  the  shortness  of  the  interval  between 
the  two  injections  would  explain  the  successful  reinfection  of 
monkeys  Nos.  4  and  5.  Xow,  however,  that  it  has  been  proved 
that  immunity,  if  present  at  all,  is  fully  developed  by  the  time  at 
which  I  reinfected  the  monkeys,  I  believe  that  after  unsuccessful 
inoculation  immunity  is  established  only  in  an  irregular  and  feeble 
manner;  Leiner  and  v.  Wiesner,  Landsteiner  and  Levaditi,  Flexner 
and  Lewis,  have  also  found  that  monkeys  which  had  been  unsuc- 
cessfully inoculated  could  be  reinfected  successfully.  At  the  same 
time  I  believe  that  immunity  does  follow  unsuccessful  intracerebral 
injection  in  some  cases  and  under  certain  conditions.  It  is  possible 
that  the  amount  of  virus  used  has  some  bearing"  on  this  matter.  As 
far  as  I  can  see,  most  experimenters  have  used  emulsion  of  spinal 
cord,  filtered  through  paper  or  centrifugalized  for  a  short  time; 
on  the  other  hand,  I  myself  have  used  the  virus  unfiltered  or  have 
merely  allowed  the  coarser  particles  to  settle.  Flexner  and  Lewis 
have  shown  in  their  later  work  that  unsuccessful  inoculation  confers 
immunity  if  large  doses  of  virus  have  been  used.  They  believe, 
further,  that  injection  of  fresh  virus  into  the  brain,  if  not  followed 
by  paralysis,  does  not  produce  immunity,  but  that  virus  preserved 
in  glycerine  does  do  so.  As  their  experience  became  more  exten- 
sive, Flexner  and  Lewis  appear  to  have  come  to  believe  that 
immunity  does  follow  unsuccessful  inoculation,  but  not  with  the 
same  certainty  as  after  successful  infection. 

For  practical  purposes  it  does  not  much  matter  whether 
unsuccessful  intracerebral  inoculation  is  followed  by  immunity; 
such  a  method  of  immunization  is  not  practicable.  But  it  is  of 
importance  to  know  whether  immunity  can  be  produced  without 
causing  the  disease.  It  was  from  this  practical  point  of  view  that 
I  called  attention  to  the  existence  of  immunity  in  some  of  my  cases 
of  unsuccessful  inoculation.  It  will  be  only  if  no  serious  symptoms 
are  caused  by  the  proceeding-  that  any  method  of  preventive 
inoculation  can  be  of  any  practical  use.  Subsequent  events  have 
given  support  to  the  optimistic  view,  which  I  adopted  on  perhaps 
somewhat  slender  grounds.  Authors,  who  at  first  denied  the 
possibility  of  such  a  thing,  have  published  methods  of  immunization 
which  confer  specific  protection  without  causing  an  attack  of  the 
disease. 


156  EPIDEMIC   INFANTILE   PARALYSIS 

I  have  already  touched  on  the  question  of  the  duration  of  the 
immunity.  Landsteiner  and  Leyaditi  showed  that  it  was  still  present 
after  twenty-five  days,  I  myself  after  forty-one  days,  Leiner  and 
v.  Wiesner  after  about  100  days,  and  Flexner  and  Lewis  found  it 
four  to  five  months  after  the  onset  of  paralysis. 

Methods  of  Immunization  in  Monkeys.— The  attempt  to  dis- 
cover a  method  of  immunizing-  monkeys  which  might  be  used  in 
human  beings  is  not  at  present  of  great  practical  importance. 
Only  a  small  number  of  the  children  exposed  to  infection  are 
affected  by  the  disease  even  in  times  of  epidemic,  and  parents  are 
not  likely  to  agree  to  preventive  inoculation  while  the  risks  are 
so  small.  On  the  other  hand,  it  is  possible  that  future  epidemics 
will  be  much  more  violent  than  they  were  in  Scandinavia;  the 
character  of  the  epidemics  has  changed  very  much  even  in  the  last 
ten  years.  If  we  consider  what  a  panic  the  disease  causes  during  an 
epidemic,  and,  further,  how  powerless  we  are  when  faced  by  the 
disease  in  its  acute  stages,  it  must  be  evident  that  it  is  not  only 
justifiable,  but  it  is  the  duty  of  experimental  science  to  carry  out 
such  investigations. 

Many  authors  have  endeavoured  to  find  the  most  effective  and 
least  dangerous  method  of  artificial  immunization  of  monkeys. 
The  experiments  are  still  in  the  initial  stages,  but  they  provide  a 
very  definite  basis  for  further  work  on  the  same  lines. 

(a)  Protective  inoculation  with  dry  virus.  Pasteur's  method 
in  rabies  depends  on  the  introduction  of  virus  which  has  been  dried 
for  different  lengths  of  time.  The  analogy  between  the  two 
diseases  led  Landsteiner  and  Levaditi  to  attempt  to  produce 
immunity  by  similar  means.  They  proceeded  exactly  according  to 
Pasteur's  method;  the  spinal  cord  of  a  monkey  with  poliomyelitis 
was  dried  over  caustic  potash  at  a  temperature  of  220  C.  for  various 
periods,  and  then  rubbed  up  in  physiological  saline  and  injected 
subcutaneously  into  the  monkeys. 

Monkeys  Nos.  36  and  37  were  treated  in  this  manner.  From  December  3 
to  December  10,  1909,  they  received  a  daily  injection  of  2  c.c.  of  the 
emulsion  made  from  the  dried  spinal  cord  in  the  following  way  :  — 

December    3,  cord  dried  for  9  days. 

4  ,,        „      „  9     ,, 

5  „        „       „  6     „ 

6  ,,         „      ,,  6     ,, 

7  „        ,,      ,,  5     >> 

8  „        „      „   5     „ 

9  „         „       .,  4      „ 
10      „        ,,       „   3     ., 

Ten  days  after  the  last  vaccination  monkey  No.  37  was  infected  together 
with  a  control  monkey  No.  51  (Cercofithecus).  The  control  became  para- 
lysed after  twelve  days,  and  died  three  days  later.  Monkey  No.  37  remained 
well. 

Monkey  36  was  infected  together  with  a  control  monkey  No.  sg 
(Macacus  cynomolgus)  nineteen  days  after  the  last  vaccination.  The  control 
was  paralysed  in  four  days  and  died  on  the  fifth.     Monkey  36  remained  well. 


THE    FIGHT     AGAINST    THE     DISEASE  1 57 

As  has  been  shown  above,  such  a  method  does  not  diminish 
the  potency  of  the  virus,  and  since  Flexner  and  Lewis  have  proved 
that  subcutaneous  injection  may  cause  paralysis,  such  a  method 
should  be  rejected  a  priori.  As  a  matter  of  fact,  Landsteiner  and 
Levaditi  found  subsequently  that  subcutaneous  injection  of  dried 
virus  does  cause  paralysis  sometimes. 

Example. — Monkey  No.  87  {Macacus  cynomolgus)  received 
on :  — 

January    27,  2  c.c.  of  virus  dried  for  21  days}  ^.     ,,      „.,     ,        ,  ,•       .  c.,  ,     • 

~J  On  the  5th,  trembling  ;  6th,  paralysis ; 

P,"         ^  "  >>        4     >)  jtfi   death  with  typical  lesions. 

February     4  ,,  ,,      24     ,,    )       '     '  }r 

Monkey  No.  86  {Macacus  cynomolgus)  received  on:  — 

January    27,  2  c.c.  of  virus  dried  for  21  days\ 

February   4  ','  ',',      24     "     [ On  February  11  paralysis  and  death. 

9  ,'.  ,',      25     „    J 

The  fact  that  the  monkeys  which  were  not  paralysed  by  the 
subcutaneous  injection  were  mainly  immune,  proves  that  if  sufficient 
quantities  of  virus  are  used  an  unsuccessful  inoculation  may  protect 
against  the  disease.     This  confirms  my  own  experience  (see  p.  155). 

(/3)  Immunization  by  small  doses  of  virulent  material.  The 
basis  of  Pasteur's  treatment  of  rabies  is  the  theory  that  the  virus 
becomes  attenuated  by  being'  dried.  At  the  present  time  there  are 
g'ood  reasons  for  believing'  that  drying"  does  not  weaken  the 
individual  particles  of  the  virus,  but  that  it  does  diminish  their 
number;  it  follows  that  in  Pasteur's  method  of  protective  inocula- 
tion the  principle  is  really  one  of  giving  a  small  dose  of  fully  active 
virus  at  first  and  later  giving  larger  and  larger  doses.  In  accord- 
ance with  this  theory,  Pasteur's  method  has  been  successfully 
modified.  It  was  natural  that  experiments  should  be  made  on  these 
lines  in  the  case  of  poliomyelitis.  Flexner  and  Lewis  carried  them 
out.     The  following  example  may  be  quoted:  — 

A    rhesus   monkey    received    subcutaneous    injections    in    the    following 
manner  :  — 

January  12  to  January  16,  1910  daily  35  c.c.  virus  of  full  virulence. 
20         ,,       23     „        „       J7    „       ,, 

27  ,,  31  „  ,,  -Ay        ,,  „ 

The   dose  was   gradually   increased;   the  monkey   received   \   c.c,    then 

1  c.c,  and  on  March  23,  1910,  it  received  5  c.c.  virus  of  full  virulence. 

On   April  2,    1910,   this   monkey  received   an   intracerebral   injection    of 

2  c.c.  of  virus  of  full  virulence  and  remained  permanently  well.  The  virus 
used  in  this  case  was  exceedingly  active  and  very  constant  in  its  action ; 
a  dose  of  even  Ticc-C-  killed  a  monkey  which  had  not  been  previously  treated, 
after  a  normal,  period  of  incubation.  A  high  degree  of  immunity  can  be 
attained  by  the  use  of  the  method  of  Flexner  and  Lewis;  in  the  example 
given  above  the  animal  was  protected  against  200  times  the  lethal  dose. 


I58  EPIDEMIC   INFANTILE  PARALYSIS 

Flexner  and  Lewis  found  later  that  one  subcutaneous  injection 
of  fully  active  virus  conferred  immunity.  This  was  similar  to  my 
own  experience,  as  in  experiment  3  (b)  described  above.  The  method 
proved  very  inconstant  in  its  action  and  dangerous,  because  many 
of  the  animals  became  paralysed  instead  of  only  immunized. 

(y)  Immunization  with  virus  attenuated  or  killed  by  chemical 
means.  Kraus  was  the  first  to  make  experiments  in  this  direction. 
By  treating-  the  virus  with  '5  per  cent,  carbolic  acid  he  believed  that 
he  had  obtained  a  safe  and  certain  vaccine.  He  reported  the 
following  experiment :  — 

On  December  18,  1909,  a  monkey  received  a  subcutaneous  injection  of 
5  c.c.  of  fresh  virus  of  full  strength;  on  January  2,  igio,  it  received  a  further 
injection  of  6  c.c.  of  post-mortem  virus  mixed  with  '5  per  cent,  carbolic  acid. 
A  second  monkey  received,  on  January  3,  1910,  6  c.c.  of  virus  mixed  with 
'5  per  cent,  carbolic  acid.  On  January  13  these  two  monkeys  and  a  control 
monkey  received  an  intracerebral  injection  of  virus  filtered  through  paper. 
The  control  became  paralysed  on  the  twelfth  day  and  died  on  the  fourteenth. 
Both  the  monkeys  which  had  been  treated  previously  remained  well. 

As  a  result  of  his  experience  with  rabies,  Kraus  lays  stress  on 
the  use  of  virus  filtered  through  paper  in  testing  the  immunity.  It 
is  not  clear  in  the  above  experiment  whether  the  immunity  of  the 
first  monkey  was  due  to  the  injection  of  the  carbolized  virus  or  of 
the  fully  virulent  virus. 

Kraus  recognized  later,  as  did  also  Leiner  and  v.  Wiesner, 
Landsteiner  and  Levaditi,  that  even  after  five  days  '5  per  cent,  of 
carbolic  acid  did  not  kill  the  virus  in  every  case  (see  p.  67),  and  that 
this  method  was  therefore  not  without  danger;  consequently,  in  his 
more  recent  experiments  he  always  used  virus  which  had  been 
rendered  harmless  by  treatment  with  1  to  ii  per  cent,  carbolic  acid 
for  six  days,  and  which  had  been  freed  from  all  coarse  particles  by 
centrifugalization  before  it  was  so  treated.  One  injection  of  virus 
prepared  in  this  way  protected  monkeys  against  subdural  infection 
carried  out  fourteen  days  to  two  months  later  with  virus  (filtered 
through  paper)  which  was  fatal  to  the  control  monkeys. 

I  made  one  unsuccessful  attempt  to  produce  immunity  by  the 
use  of  virus  killed  with  formalin. 

Monkey  No.  35  (Macacus  rhesus)  was  given  an  intracerebral 
injection  of  virus  treated  with  formalin  on  February  26  without 
result. 

On  March  22  this  monkey,  together  with  a  control  monkey  Xo.  43,  was 
infected   with   virus    Xo.    12    (intracerebral,    "6   c.c;    intraperitoneal,  3    c.c). 
Course  of  the  infection  :  — 
Monkey  Xo.   35  :  — 
March  23-April  26. — Xo   symptoms. 
April  7. — Weak  in  the  hind  limbs. 

April  8. — Definite  flaccid  paresis  of  both  hind  limbs  and  the  left  arm. 
April  9. — Paresis  more  marked. 
April  10-15. — Xo  change. 


THE    FIGHT    AGAINST     THE     DISEASE  1 59 

April  16.— Both  arms  markedly  paretic;  both  hind  limbs  completely 
paralysed. 

April   ig. — Died  with  increasing  paralysis. 

Microscopical  appearances  typical. 

Monkey    Xo.    43  :  — 

March   23-April  4. — Xo   symptoms. 

April  4. — Depressed ;  does  not  want  to  climb. 

April  5. — Marked  paralysis  of  all  limbs. 

April  6.— Death. 

Microscopical  appearances  typical. 

(8)  Immunization  with  heated  virus.  If  any  method  of  pro- 
tective inoculation  is  ever  used  it  will  have  to  be  one  which  can 
be  guaranteed  to  be  harmless.  The  monkey  is  an  animal  which 
shows  unmistakably  the  lesions  of  poliomyelitis  after  intracerebral 
inoculation.  Although  we  did  not  succeed,  we  aimed  at  finding  a 
virus  which  would  confer  immunity  and  yet  be  harmless  when 
injected  into  the  brain  of  monkeys.  For  this  purpose  we  studied 
virus  which  had  been  subjected  to  high  temperatures.  On  page  65 
we  have  already  given  some  of  our  results.  Intracerebral  injection 
of  virus  which  had  been  heated  for  half  an  hour  at  ^l=)°  and  at  500 
proved  harmless  to  monkeys:  when  heated  at  450  the  virus  was 
less  active.  Subcutaneous  injection  of  virus  heated  to  45°,  500,  or 
550  was  quite  harmless.  Monkeys  treated  with  virus  prepared  by 
these  methods  were  tested  in  many  ways. 

Experiment  1. — The  following  monkeys  received  intracerebral  injec- 
tions of  '6  c.c.  of  virus  Xo.   11  on  March  15,  igio  :  — 

{a)  Control  monkey  Xo.  41  (Macacus  rhesus).  Paralysed  on  the  26th. 
Recovered.     (Details  on  p.  59). 

(b)  Monkey  Xo.  32  (Macacus  rhesus),  which  suffered  on  Februarv  7, 
1910,  from  paralysis  caused  by  intracerebral  injection  of  virus  heated  to 
450  (see  p.  65).  After  the  infection  on  March  15  no  symptoms  observed  for 
two  months. 

(c)  Monkey  Xo.  34  [Macacus  rhesus)  received  subcutaneous  injections 
of  2  c.c.  of  virus  heated  to  450  on  February  7  and  9. 

Result  of  the  infection  on  March  15. — Xo  paralysis;  died  of  secondary 
infection  on  the  22nd. 

Xo  lesions  of  poliomyelitis  could  be  found. 


Experiment    2. — The    following    monkeys    received    intracerebral    injec- 
tions of  '6  c.c.  of  virus  Xo.   11  on  May  31,  1910. 

(a)  Control  monkey  Xo.   58  (Macacus  rhesus). 
May  31-June   10. — Xo  symptoms. 

June   11. — Paralysed. 

June  13. — Death.     Typical  microscopical  appearances.     For  details,  see 
P-  77)- 

(b)  Monkey  Xo.   51    (Macacus  rhesus)  had  had  an  intracerebral  injection 
of  virus  heated  to  500  with  no  result  on  April  25,   1910  (cf.  p.  65). 

Result  of  the  infection  of  May  31. — Remained  permanentlv  well. 

(c)  Monkey  Xo.    52    (Macacus  rhesus)  received  a  subcutaneous  injection 
of  virus  heated  to  500  on  April  25,   1910,  without  result. 

Result  on  infection  on  May  31. — Remained  permanentlv  well. 


l6o  EPIDEMIC  INFANTILE  PARALYSIS 

The  other  monkeys  treated  without  result  with  virus  heated  to  50°, 
monkey  No.  53  (3  c.c.  on  April  25,  27  and  29,  subcutaneously),  and  monkey 
No.  54  (daily  from  April  25  to  April  30,  3  c.c.  subcutaneously),  died  of 
pulmonary  tuberculosis  before  their  immunity  could  be  tested. 


Experiment  3. — The  following  monkeys  received  an  intracerebral  injec- 
tion of  '6  c.c.  of  virus  No.   12  on  March  2,  igio  : — ■ 

(a)  Control  monkey  No.  37  (Macacus  rhesus). 
March  9. — Totally  paralysed. 

Gradually  recovered   (see  p.    57). 

(b)  Monkey  No.  27  (Mangabey)  received  5  c.c.  of  virus  heated  to  550 
subcutaneously  on  January  25  and  January  29  without  any  result. 

Result  of  the  infection  on  March  2,  1910  :  — 

March  11. — Depressed. 

March  13. — Cerebral  symptoms. 

March  14. — Death  from  cerebral  paralysis.      (For  details,  see  p.  53.) 

[Two  other  monkeys  inoculated  with  virus  heated  to  550  unfortunately 
died  of  intercurrent  disease  before  their  immunity  could  be  tested.  Monkey 
No.  28  received  a  subcutaneous  injection  of  5  c.c.  on  January  25  and  January 
29  with  no  effect;  monkey  No.  26  intracerebral  injection  of  '5  c.c.  on  the 
25th  without  result.] 

These  experiments,  which  must  be  confirmed,  seem  to  show 
that  virus  heated  to  550  is  quite  harmless,  but  no  longer  has 
sufficient  immunizing  power.  Landsteiner  and  Levaditi  had  the 
same  experience.  Monkeys  treated  by  subcutaneous  injection  with 
virus  heated  to  550  for  half  an  hour  succumbed  to  infection  caused 
nine  days  after  the  last  preventive  inoculation;  the  infection  appears 
to  have  been  of  a  severe  type. 

Virus  heated  to  450  for  half  an  hour  proved  to  have  definite 
immunizing  power,  but  not  to  conform  to  the  necessary  degree  of 
safety  (cf.  experiments  recorded  on  p.  65). 

Virus  heated  to  500  seems  to  meet  the  requirements  of 
immunizing  power  and  safety  better  than  the  others.  Further 
experiments  with  this  virus  may  lead  to  more  hopeful  results. 

(e)  Immunization  with  mixtures  of  virus  and  serum  containing 
antibodies.  As  we  shall  see  later,  it  is  possible  to  demonstrate  the 
presence  of  antibodies  in  the  serum  of  immune  monkeys  and  human 
beings  which,  when  mixed  with  virus  in  vitro,  destroy  the  activity 
of  the  latter.  It  was  natural  to  attempt  to  produce  immunity  by  the 
injection  of  such  mixtures.  I  have  had  some  success  in  this  direc- 
tion. Flexner  and  Lewis  obtained  no  result  in  similar  experiments, 
and  so  I  wish  to  emphasize  the  fact  that  the  following  experiments 
are  the  only  ones  performed  by  me  along  these  lines  and  that  they 
were  not  performed  ad  hoc. 

Experiment    1. — The    following   monkeys   were    given    an    intracerebral 
injection  of  '6  c.c.  of  virus  No.   11  on  March  15,  1910  :  — 
(a)  Control  monkey  No.  41   (Macacus  rhesus). 
March  16-25. — No  symptoms. 
March  26. — Paralysed. 


THE    FIGHT    AGAINST    THE    DISEASE  l6l 

March  28. — Paralysis  more  marked;  then  gradual  improvement. 
(Details,  see  p.   59). 

(b)  Monkey  No.  30  (Macacus  rhesus)  had  received  an  intracerebral 
injection  of  a  mixture  of  virus  and  specifically  active  serum,  without  any 
subsequent  symptoms,  on  February  7,  1910. 

Result  of  the  injection  on  March  15,  1910. — Remained  permanently  well. 

(c)  Monkey  No.  31  {Macacus  rhesus)  received  the  same  preliminary 
treatment  as  monkey  No.   30. 

Result  of  infection  on  March  15. — Remained  permanently  well. 


Experiment  2. — The  following  monkeys  were  given  an  intracerebral 
injection  of  '6  c.c.  of  virus  No.  11  on  July  13,  1910  :  — 

(a)  Control  monkey  No.   102   (Macacus  rhesus). 
July  13-24.— Well. 

July  25. — Paralysed. 

July  26. — Death.    Microscopical  appearances  typical.    (Details  on  p.  77.) 

(b)  Monkey  No.  57  (Macacus  rhesus)  had  received  an  intracerebral 
injection  of  a  mixture  of  virus  and  human  serum  containing  antibodies  on 
May  31,  1910. 

Result  of  the  infection  on  July  13. — Remained  permanently  well. 

(c)  Monkey  No.  60  (Macacus  rhesus)  had  received  an  intracerebral 
injection  of  a  mixture  of  virus  and  serum  containing  antibodies  (see  p.   171). 

Result  of  the  infection  on  July  13. — Died  on  July  30  as  a  result  of 
a  cerebral  abscess  (see  p.  52). 

It  is  remarkable  that  no  changes  indicative  of  poliomyelitis  were  found 
in  this  animal  even  on  July  30.      (The  control  had  died  on  July  26.) 


Experiment  3. — On  May  31,  1910,  the  following  monkeys  were  given 
an  intracerebral  injection  of  '5  c.c.  of  virus  No.  11  :  — 

(a)  Control  monkey  No.  58  (Macacus  rhesus). 
June  1-6. — No  symptoms. 

June  11. — Paralysed. 

June  13. — Death.    Microscopical  appearances  typical.    (Details  on  p.  77.) 

(b)  Monkey  No.  39  (Macacus  rhesus)  received  an  injection  of  a  mixture 
of  virus  and  monkey's  serum  containing  antibodies  on  March  2,  1910, 
without  any  subsequent  symptoms  (see  p.   164). 

Result  of  infection  on  May  31. — Remained  permanently  well. 

In  my  experiments,  "therefore,  four  monkeys  (if  monkey  No.  60 
is  counted  the  number  is  five),  which  had  previously  received  an 
injection  of  a  mixture  of  virus  and  serum  containing  antibodies,  sur- 
vived an  infection  which  produced  paralysis  in  the  controls  in  the 
usual  way.  Landsteiner  and  Levaditi  obtained  the  same  result  with 
a  monkey  which  had  been  inoculated  with  such  a  mixture  subcu- 
taneously;  the  animal  was  found  to  be  protected  against  reinfection, 
while  two  control  monkeys  became  paralysed. 

Flexner  and  Lewis  say  that  they  were  unable  to  produce 
immunity  with  a  mixture  of  virus  and  serum ;  they  suppose  that  the 
serum  prevents  that  development  of  the  virus  which  is  necessary 
for  the  production  of  immunity.  As  far  as  I  can  judge  from  the 
communications  of  these  authors,  the  monkeys  which  they  tested 
had  been  vaccinated  with  serum  obtained   from   highly   immunized 

11 


1 62  EPIDEMIC   INFANTILE  PARALYSIS 

monkeys.  But  it  is  well  known  that  the  proportion  of  virus  to 
antibody  is  of  the  greatest  importance  for  success  in  serum- 
vaccination.  In  my  experiments,  in  which  serum  from  convalescent 
cases  was  used,  a  small  quantity  only  of  antibody  was  present  in 
all  probability,  and  thus,  by  chance,  favourable  conditions  prevailed. 

(£)  Immunization  during  the  incubation  period.  Protective 
inoculation  against  rabies  stands  in  a  unique  position  compared  with 
inoculation  against  other  diseases,  in  that  it  is  used  after  infection 
has  taken  place,  i.e.,  during  the  incubation  period  of  the  disease. 
That  this  is  possible  is  explained  by  the  difference  between  the  virus 
which  causes  hydrophobia  and  the  virus  fixe,  used  for  vaccination. 
Landsteiner  and  Levaditi,  following  Pasteur's  method,  tried  to 
protect  monkeys  after  they  had  been  given  an  intracerebral  injection 
of  virus.  These  animals,  however,  all  became  paralysed  on  the 
eighth  day,  like  the  controls. 

Following  the  same  train  of  thought,  Flexner  and  Lewis  tried 
to  immunize  monkeys  by  giving  simultaneously  an  intracerebral 
injection  of  fully  active  virus  and  a  subcutaneous  injection  of  virus 
heated  to  6o°  for  half  an  hour,  or  of  virus  heated  to  55°-57°  for  one 
hour.  These  experiments  were  without  result.  The  same  thing 
happened  in  Krause's  experiments;  simultaneously  with,  or  after, 
intracerebral  injection  he  gave  monkeys  his  carbolic  acid  vaccine. 
Attempts  to  immunize  monkeys  during  the  incubation  period  have 
failed  so  far. 

(rj)  The  biological  connection  between  poliomyelitis  and  rabies 
from  the  point  of  view  of  immunity.  Owing  to  the  apparently  close 
relationship  between  the  active  agents  of  rabies  and  poliomyelitis, 
and  because  of  the  many  analogies  between  the  diseases,  Land- 
steiner and  Levaditi  tried  to  find  out  whether  there  was  any 
biological  connection  between  them  from  the  point  of  view  of 
immunity. 

Rhesus  No.  6  had  been  proved  immune  to  reinfection  after  having 
survived  an  attack  of  poliomyelitis,  and  its  serum  contained  antibody. 
On  May  17  '25  c.c.  of  rabies  virus  (virus  fixe)  was  injected.  After  nine 
days  the  animal  became  paralysed,  and  died  on  May  29.  The  course  of  the 
disease  was  the  same  in  the  control. 

This  experiment  proves  the  essential  biological  difference 
between  the  two  diseases  in  spite  of  the  many  points  of  analogy 
between  them. 

II.— SPECIFIC  ANTIBODIES. 

Fixation  of  Complement.— It  is  usual  to  demonstrate  the 
presence  of  specific  antibodies  in  the  blood  of  cases  of  acquired 
immunity.  It  is  very  difficult  to  be  successful  in  the  case  of  polio- 
myelitis because  the  cause  of  the  disease  cannot  be  cultivated,  and 
a  large  number  of  reactions,  which  ordinarily  are  carried  out  in  a 
test    tube,    are    impossible.     We    ourselves    began    by    testing    the 


THE    FIGHT     AGAINST    THE     DISEASE  163 

reaction  of  fixation  of  complement,  because  this  is  one  of  the  most 
sensitive  reactions  and  serves  to  indicate  extremely  small  quantities 
of  antigen  and  antibodies. 

We  used  the  ordinary  procedure;  as  indicator  we  used  the 
known  hemolytic  system  (1  c.c.  of  5  per  cent,  sheep's  blood 
corpuscles,  well  washed;  specific  hsemolytic  amboceptor  obtained 
from  rabbits  in  twice  the  necessary  amount,  and  fresh  guinea-pig 
serum  as  complement,  also  in  twice  the  necessary  amount).  Extracts 
of  the  spinal  cord  of  monkeys  and  human  beings,  who  were  certainly 
suffering  from  poliomyelitis,  were  used  as  antigen ;  we  used  not  only 
watery  extracts,  but  also  antiformin  extracts.  We  made  use  of  the 
•experience  gained  by  Altmann  and  Schulz  in  making  the  antiformin 
-extracts  (Zeitsch.  f.  Immunitatsforschung,  vol.  iii).  We  examined 
the  blood  and  cerebrospinal  fluid  of  human  beings  in  various  stages 
of  the  disease  for  antibodies  which  would  fix  the  complement;  we 
also  examined  the  serum  of  monkeys  which  had  survived  infection, 
and  of  monkeys  which  had  received  repeated  large  doses  of  virus 
for  purposes  of  immunization.  I  will  only  mention  summarily 
that  the  existence  of  antibodies  which  would  fix  the  complement  was 
not  proved  in  a  single  case.  We  did  obtain  fixation  of  the  comple- 
ment by  mixing  the  watery  extract  with  the  serum  of  a  sheep  which 
had  been  treated  many  times  with  poliomyelitic  spinal  cord.  How- 
ever, the  serum  of  this  sheep  showed  fixation  of  the  complement 
when  mixed  with  a  similar  extract  of  the  spinal  cord  of  a  normal 
monkey,  so  that  the  occurrence  of  fixation  of  the  complement  was 
■due  merely  to  a  specific  reaction  between  the  albumin  of  the  sheep's 
serum  and  of  the  monkey's  spinal  cord,  and  it  was  not  a  reaction 
specifically  of  the  virus  of  poliomyelitis.  Starr  and  Wollstein  had 
already  examined  the  spinal  fluid  of  a  large  number  of  patients  with 
the  same  result.  They  used  spinal  cord,  nerves,  muscles  and 
•extract  of  the  liver  from  cases  of  poliomyelitis  as  antigen. 

Specific  HypersensitiveneSS. — We  have  investigated  the  ques- 
tion whether  there  is  any  specific  hypersensitiveness  shown  by  cases 
of  experimental  poliomyelitis  analogous  to  the  tuberculin  reaction. 
We  investigated  the  skin  particularly.  We  had  found  that  in  tuber- 
culosis the  method  of  subcutaneous  injection  gave  very  reliable 
results.  We  injected  into  the  skin  of  monkeys  during  the  incubation 
period,  directly  paralysis  set  in  and  during  convalescence,  2  c.c.  of 
a  5  per  cent,  emulsion  of  monkey's  spinal  cord  containing  living  or 
dead  (55°)  virus.  We  never  had  any  positive  result.  Leiner  and 
v.  Wiesner  also  had  negative  results  by  this  method. 

These  negative  results  in  the  search  for  specific  antibodies  are 
of  importance,  because  they  constitute  another  analogy  between 
poliomyelitis  and  rabies.  In  rabies  the  reaction  of  fixation  of  com- 
plement has  never  been  obtained  even  when  serum  has  been  used 
which  has  been  proved,  by  other  methods,  to  contain  antibodies. 

Successful  Demonstration  of  Antibodies.— The  antibodies  in 
rabies  have  been  demonstrated  by  mixing  the  virus  with  the  serum 
•of  individuals  who  have  undergone  specific  treatment.     On  injection 


164  EPIDEMIC  INFANTILE  PARALYSIS 

of  this  mixture,  under  certain  conditions,  it  is  found  to  be  non- 
virulent  to  certain  sensitive  animals.  The  necessary  conditions  are, 
that  the  emulsion  should  be  as  finely  divided  as  possible  (i.e.,  passed 
repeatedly  through  filter  paper),  and  that  contact  between  the  virus 
and  the  serum  should  be  sufficiently  long. 

I  mixed  virus  from  poliomyelitic  spinal  cord,  usually  of  a 
strength  of  5  per  cent,  and  repeatedly  filtered  through  paper,  with 
equal  parts  of  the  serum  to  be  investigated;  the  mixture  was  kept 
for  one  hour  at  a  temperature  of  37°.  and  then  for  twenty-three 
hours  in  an  ice-chest  or  at  the  temperature  of  the  room.  The 
mixture  was  given  to  monkeys  as  an  intracerebral  injection  of  "6  or 
•8  c.c.  The  control  experiments  were  made  with  a  similar  mixture 
prepared  with  serum  from  a  normal  monkey;  the  mixture  was 
allowed  to  stand  for  the  same  length  of  time,  and  the  same  doses 
were  given  to  normal  monkeys  by  intracerebral  injection.  The 
results  were  as  follows  :  — 

Experiment  1. — The  following  monkeys  received  intracerebral  injections 
of  '7  c.c.  of  a  mixture  of  serum  and  virus  Xo.   12  prepared  as  above  :  — 

(a)  Control  monkey  Xo.  29  {Macacus  rhesus).  A  mixture  containing 
serum  of  a  normal  monkey. 

February  8-14. — Xo  symptoms. 

February  15. — Paralysis,  which  ended  in  death  on  the  22nd.  (Details, 
see  p.  47-) 

(b)  Monkey  X'o.  30  (Macacus  rhesus).  The  virus  was  mixed  with  serum 
withdrawn  on  February  5  from  monkey  Xo.  6,  which  had  repeatedly  been 
proved  to  be  immune  to  reinfection  (see  pp.   151  and  152). 

Result  of  the  infection  on  February  7. — Monkey  Xo.  3  remained  per- 
manently well. 

(c)  Monkey  Xo.  31  (Macacus  rhesus).  The  virus  was  mixed  with  an 
equal  part  of  a  mixture  of  the  sera  of  monkeys  Xos.  9  and  10  (equal  parts), 
which  had  been  proved  to  be  immune  (see  p.  152). 

Result  of  the  infection  on  February  7. — Monkey  Xo.  31  remained  per 
manentlv  well. 


Experiment  2. — On  March  2,  1910,  the  following  monkeys  received  ai> 
intracerebral  injection  of  a  mixture  of  serum  with  virus  Xo.  12  ('6  c.c.)  :  — 

(a)  Control  monkey  Xo.  37  (Macacus  rhesus).  The  serum  of  a  normal 
monkey  was  used. 

March  3-8. —Well. 

March  9. — Paralysed. 

March  11. — Total  paralysis  of  the  hind  limbs. 

April  14. — Death  from  marasmus.      (Details,  see  p.  57.) 

(b)  Monkey  Xo.  38  (Macacus  rhesus).  The  virus  mixed  with  serum 
from  monkey  Xo.  27,  which  had  been  unsuccessfully  inoculated  with  killed 
virus  (see  pp.  53  and  160). 

March  3-9. — Xo  symptoms. 

March  10.— 111. 

March  11. — Paralysed. 

March   12. — Death.      (Details,  see  p.    54.) 

(c)  Monkey  Xo.  39  (Macacus  rhesus).  Virus  mixed  with  sera  of 
monkeys  Xos.  32  and  34.    Monkey  Xo.  32  had  survived  infection  on  February 


THE    FIGHT    AGAINST    THE    DISEASE  1 65 

7,  1910,  and  consequent  paralysis  (see  p.  65);  it  was  immune  against  re- 
infection (see  p.  159).  Monkey  No.  34  had  received  subcutaneous  injections 
of  virus  heated  to  45°  on  February  7  and  9  for  immunizing  purposes. 

Result  of  the  injection  on  March  2. — Monkey  No.  39  remained  per- 
manently well. 

These  experiments  show  that  serum  from  monkeys,  which 
have  survived  paralysis  or  which  have  been  successfully  immunized, 
when  mixed  with  virus  under  these  conditions,  will  destroy  the 
infective  power  of  the  virus. 

Landsteiner  and  Levaditi,  Leiner  and  v.  Wiesner,  Flexner  and 
Lewis  have  proved  by  similar  methods  that  specific  antibodies  are 
present  in  antipoliomyelitic  serum.  Certain  differences  in  the 
methods  used,  and  particularly  in  the  duration  of  contact  between 
the  virus  and  the  serum,  make  it  necessary  to  refer  more  in  detail 
to  these  experiments.  In  the  first  place  those  of  Landsteiner  and 
Levaditi :  — 

Experiment  1. — 3  c.c.  of  the  serum  of  immunized  monkeys,  the 
immunity  of  which  had  been  tested,  were  mixed  with  35  c.c.  of  virus 
emulsion  filtered  through  paper;  the  mixture  was  allowed  to  stand  for 
four  hours  at  the  room  temperature  and  was  then  injected  into  the  following 
animals  :  — 

(a)  Control  mandril  No.  73  (virus  mixed  with  saline),  paralysed  in 
thirteen  days,  dead  in  fifteen  days. 

(b)  Macacus  rhesus  No.  74  (virus  mixed  with  serum  from  immune 
monkey). 

Remained  permanently  well. 

In  the  second  experiment  serum  and  virus  were  mixed  in  the  same  way, 
but  the  mixture  was  allowed  to  stand  on  ice  for  a  night  [i.e.,  at  least  twelve 
hours).     It  was  injected  into  the  following  :  — 

(a)  Control  monkey  No.  go  {Macacus  cynomolgus),  virus  mixed  with 
saline;  paralysed  in  nine  days;  microscopical  appearances  typical. 

(b)  Macacus  cynomolgus  No.  88.  Virus  mixed  with  immune  serum. 
Remained  well. 

(c)  Macacus  cynomolgus  No.  89.  "Virus  mixed  with  immune  serum. 
Remained  well. 

Leiner  and  v.  Wiesner  found  that  when  a  mixture  of  virus  and 
immune  serum  was  kept  for  four  hours  at  the  temperature  of  the 
room,  the  intracerebral  injection  caused  only  slight  paresis  in 
monkeys,  while  control  animals  became  severely  ill.  After  contact 
of  virus  and  serum  for  six  hours  the  monkeys  remained  well  and 
the  controls  became  ill. 

Flexner  and  Lewis  proved  that  normal  monkey  serum  mixed 
with  the  virus  had  no  effect  upon  it,  but  that  immune  serum  added 
to  virus,  the  mixture  being-  warmed  for  one  hour  at  370  and  allowed 
to  stand  on  ice  overnight,  rendered  the  virus  innocuous.  This  was 
practically  a  corroboration  of  my  own  experiments. 

The  unanimous  verdict  of  all  these  authors  is  that  the  serum  of 
monkeys  which  have  survived  the  disease,  or  which  have  been 
successfully   immunized  against   it,    when   mixed   with   virus    for   a 


1 66  EPIDEMIC   INFANTILE   PARALYSIS 

sufficiently  long  time  renders  the  latter  completely  innocuous.  We 
do  not  know  how  the  serum  produces  this  result.  Some  authors 
talk  simply  of  an  "  antimicrobial  "  serum;  but  we  know  of  no  means 
to  prove  that  the  serum  kills  the  virus  in  the  test-tube.  The  only 
reagent  which  we  possess  is  the  body  of  the  living  monkey.  It  is 
possible  that  the  virus  is  killed  in  the  test-tube,  but  it  is  also  possible 
that  it  is  not  killed  at  all.  but  merely  rendered  non-infective  because 
its  reproductive  power  is  destroyed.  It  is  going  too  far  to  say  that 
the  serum  is  "antimicrobial."  However,  it  is  quite  certain  that 
the  antipoliomyelitic  serum  prevents  infection  in  some  specific  way. 

In  this  instance  also  we  find  that  the  correlation  of  results 
obtained  in  different  laboratories  enables  us  to  formulate  definite 
general  conclusions  and  renders  unnecessary  the  long  series  of 
experiments  on  various  animals,  which  Krause  and  Aleinicke 
consider  to  be  essential. 

It  is  probable  that  the  antibodies  are  the  cause  of  the  immunity; 
from  the  above  experiments  we  see  that  only  sera  obtained  from 
immune  animals  proved  capable  of  abolishing  the  infectiveness  of 
the  virus;  serum  from  normal  monkeys,  or  those  in  which  pre- 
ventive inoculation  had  proved  unsuccessful,  did  not  have  this  action 
(cf.  my  experiment  2  (b)). 

Flexner  and  Clark  found  antibodies  in  the  cerebrospinal  fluid 
sometimes,  usually  just  after  recovery  from  infection.  They  hold 
that  this  is  due  to  the  abnormal  permeability  of  the  diseased  vessels. 
According  to  their  observations,  specific  antibodies  are  present  also 
in  the  bile  of  immune  monkeys. 

Flexner  and  Lewis  examined  the  serum  of  other  animals 
(horses,  rabbits  and  fowls),  but  found  that  it  had  no  effect  on  the 
activity  of  the  virus.  The  natural  immunity  which  these  animals 
show  towards  the  virus  of  poliomyelitis  therefore  cannot  be  due  to 
the  presence  of  specific  antibodies  in  their  blood.  Flexner  and 
Lewis  found  that  normal  sheep's  serum  was  slightly  active,  and 
they  believed  that  they  increased  its  activity  by  specific  treatment 
of  the  animals.  Krause  proved  that  the  serum  of  a  sheep  which 
had  been  treated  subcutaneously  for  months  with  emulsion  of  polio- 
myelitis virus,  had  a  specific  antipoliomyelitic  action  (the  degree  of 
activity  appears  to  have  been  small). 

Serum  Diagnosis. — Possessing  as  we  do  a  method  of  demon- 
strating the  presence  of  antibodies,  it  becomes  possible  to  make  the 
attempt  to  use  it  for  diagnostic  purposes.  The  first  question  which 
must  be  decided  is,  whether  antibodies  are  present  in  the  serum  of 
patients  who  have  had  Heine-Aledin  disease.  I  performed  the 
following  experiments  with  human  serum  in  conjunction  with 
Professor  Eduard  Muller,  who  consents  to  the  publication  of  the 
results  in  this  place. 

Y\  e  first  made  the  following  experiment :  The  mixtures  ^i 
virus  and  serum  were  made  in  an  exactly  similar  way  to  that  used 
in  my  experiments  with  monkeys.  The  control  serum  used  was 
taken  from  a  new-born  child,  whose  mother's  past  history  contained 
no  indication  of  poliomyelitis. 


THE     FIGHT     AGAINST     THE     DISEASE  1 67 

Experiment  1. — On  May  19,  1910,  the  following  monkeys  received  intra- 
cerebral injections  of  mixtures  of  virus  and  serum  :  — 

(a)  Control  monkey  Xo.  56  (Macacus  rhesus)  was  given  '4  c.c.  of 
emulsion  of  virus  and  '4  c.c.  of  serum  of  the  new-born  child  intracerebrally, 
and  simultaneously  5  c.c.  of  emulsion  of  virus  intraperitoneally. 

May  20-June  1. — Xo  symptoms. 

June  2. — Paralysed. 

June  10. — Death  (see  p.   76). 

(b)  Monkey  Xo.  55  (Macacus  rhesus)  injected  in  a  similar  manner.  The 
serum  of  the  patient,  Alois  H.,  was  used  in  the  mixture. 

Result  of  the  injections. — Monkey  Xo.  55  remained  permanently  well. 

A  resume  of  the  history  of  Alois  H.,  aged  23  years  (after  Ed.  Muller)  :  — 

The  child  became  ill  on  September  10;  fever,  rapid  pulse,  vomiting, 
headache,  and  constipation.  He  cried  out  when  taken  hold  of  :  "  Leave  me 
alone,  that  hurts,"'  or  even  when  he  was  only  touched.  There  was  marked 
sweating.  At  first  the  case  was  diagnosed  as  rickets  and  intestinal  catarrh. 
During  the  first  few  days  the  child  appeared  to  have  difficulty  and  pain  on 
micturition. 

October  11. — Eyes  and  cranial  nerves  normal.     Internal  organs  normal. 

Complete  flaccid  paralysis  of  both  arms  and  both  legs,  said  to  have 
appeared  on  the  second  day  of  the  illness.     Deep  reflexes  absent  in  all  limbs. 

Abdomen  is  soft.      Epigastric  reflexes  absent. 

Can  sit  up  only  with  difficulty,  the  head  rolling  in  all  directions. 

Swab  from  the  throat  shows  mainly  pneumococci,  a  few  colonies  of 
Staphylococcus  aureus.  Leucocyte  count  3,000;  blood-film  shows  nothing 
abnormal. 

Lumbar  puncture:  Clear,  colourless  fluid  under  high  pressure; 
albumin  and  sodium  chloride  present  in  large  amount ;  microscopically  a 
few  lymphocytes ;  cultures  made  from  the  fluid  all  remained  sterile. 

Within  a  week  the  general  condition  improved ;  the  child  remained 
apathetic.  Appetite  good ;  there  was  a  tendency  to  vomiting  and  a  remark- 
ably frequent  pulse.  After  three  weeks  a  scarlatiniform  rash  appeared 
suddenly  on  the  chest  and  arms ;  no  sore  throat,  no  rise  of  temperature. 
Eight  days  later  the  rash  appeared  on  the  thighs  and  disappeared  completely 
five  days  later.  Definite  peeling  in  small  flakes  was  seen  on  the  parts 
affected.  Sweating  remained  profuse.  The  condition  of  the  nervous  system 
remained  practically  unchanged;  some  improvement  in  the  arms;  the  hands 
and  fingers  showed  some  return  of  voluntary  movement.  At  the  end  of  six 
weeks,  some  distal  improvement  in  the  legs.     Xo  reaction  of  degeneration. 

The  flaccid  paralysis  of  the  legs  remained,  and  the  child  died  in  a 
marasmic  condition  at  the  end  of  May,   1910. 


Experiment  2. — On  July  13,  1900,  the  following  monkeys  were  injected 
with  mixtures  of  virus  and  serum  :  — 

{a)  Control  monkey  Xo.  102  (Macacus  rhesus).  Virus  mixed  with 
physiological  saline. 

July  14-24. — Well. 

July  25. — Paralysed. 

July  26. — Death  (see  p.  77). 

(b)  Monkey  Xo.  63  {Macacus  rhesus).  Virus  mixed  with  serum  of 
Elfrida  G.      The  serum  was  withdrawn  on  June  23  and  kept  on  ice. 

Result  of  the  injection  on  July  13  :  Monkey  Xo.  63  remained  per- 
manently well. 


1 68  EPIDEMIC  INFANTILE   PARALYSIS 

(c)  Monkey  Xo.  64  [Macacus  rhesus).  Virus  mixed  with  serum,  of 
Heinrich  P. 

Result  of  the  injections  on  July  13  :  Monkey  Xo.  64  remained  per- 
manently well. 

Short  abstract  of  the  clinical  histories  of  the  two  patients  :  — 

(1)  Elfrida  G.,  8  years  old,  from  Liidenscheid,  suffered  from  infantile 
paralysis  at  the  age  of  two.  In  Xovember,  1908,  tendon  transplantation 
performed. 

Condition  on  June  23,  1910  :  Internal  organs  normal.  The  whole  right 
leg  atrophic;  power  and  muscular  tone  diminished.  The  limb  feels  cold; 
the  patellar,  Achillis  and  plantar  reflexes  are  absent  on  the  right  side. 
Epigastric  reflexes  present.  Power  of  abdominal  muscles  good.  Talipes 
equinus  on  the  right  side  with  inversion  of  the  foot  (paralysis  of  the  peronei). 
Xo  sensory  loss. 

Diagnosis  :      Old-standing  spinal  infantile  paralysis. 

(2)  Heinrich  P.,  5  years  old;  from  Frankenau. 

In  September,  1909,  bilateral  complete  flaccid  paralysis  of  the  legs. 
(Details  may  be  found  in  Muller's  monograph,  p.  36.)  By  Xovember  the 
paralysis  had  disappeared ;  tone  of  the  muscles  good ;  plantar  reflex  present. 
Infantile  paralysis  recovered   from. 

Our  experiments  show  in  the  first  place  that  normal  human 
serum  has  no  effect  on  the  virus,  but  that  the  serum  of  individuals 
who  have  survived  an  attack  of  Heine-Medin  disease  contains  specific 
antibodies  just  as  in  the  case  of  monkeys.  Antibodies  are  present 
even  when  the  paralysis  is  completely  cured,  and  even  so  long  as 
six  years  after  the  acute  illness. 

Netter  and  Levaditi  have  paid  particular  attention  to  this  last 
point.  They  allowed  their  mixtures  of  virus  and  serum  to  stand  for 
three  hours  at  a  temperature  of  150  and  for  twelve  hours  on  ice. 

In  their  experiments  serum  was  taken  from  the  following 
patients  :  — 


(a)   Girl,  aged  3  years,  H.-M.  disease  middle  of  January,  iqiO\  T    .       .         f    . 
)i\    «-•  i         a  J  tj    at  j-  j    1  t\         u        Z.  „ I  Iniection  of  virus 

16)    Girl,  aged  7.  years,  H.-M.  disease  end  of  December,  1909        J  , 
/  \    u  j  "io  ,,    „     ,•  ...         c  c     j.  „   I    and  serum  mix- 

ic)    Man,  aged  35  years,  H.-M.  disease  beginning  or  beptem-  >    .  ,T       , 

w  !  „  t>  &  r  ture  on  ;\Tarch  9 

ber,  1909 

{d)  Boy,  aged  5  years,  H.-M.  disease  in  1907 


1 910. 


Result. — Control  monkey  Xo.  66  (virus  mixed  with  normal  serum), 
paralysed  in  seventeen  days,  dead  on  March  30. 

Monkeys  injected  with  virus  mixed  with  serum  obtained  from  cases 
[a)  to  [d)  all  remained  well. 

The  experiments  show  that  antibodies  are  present  six  weeks 
after  the  acute  illness,  and  that  they  are  still  demonstrable  after 
three  years.  Xetter  and  Levaditi  arrive  at  the  following  important 
conclusion:  The  virus  was  obtained  from  Landsteiner,  i.e.,  from 
the  Austrian  epidemic,  while  the  antibodies  were  present  in  the 
serum  taken  from  patients  in  France.  The  activity  of  the  anti- 
bodies against  the  Austrian  virus  shows  that  the  active  agent  in 
the  two  epidemics  was  the  same.  Case  (d)  was  a  so-called  sporadic 
case,  and  yet  the  serum  promptly  neutralized  the  virus.  This  affords 
the  final  proof  that  the  sporadic  and  the  epidemic  cases  belong  to 


THE    FIGHT    AGAINST     THE     DISEASE  1 69 

identically  the  same  disease.  Our  own  experiment  2  (b)  proved  the 
same  point,  the  serum  being-  derived  from  a  sporadic  case.  These 
experiments  also  prove  that  the  demonstration  of  antibodies  may 
be  used  as  a  clinical  test. 

Netter  and  Levaditi  give  the  further  interesting  facts  in  rela- 
tion to  the  question  of  the  persistence  of  the  antibodies  in  human 
beings  :  — 

Monkeys  were  injected  in  a  similar  manner  as  in  the  preceding  experi- 
ments with  serum  from  the  following  cases  :  — 

[a)  Boy,  aged  6i  years,  H-M  disease  middle  of  January,  1910  | 
(/>)   Boy,  aged  12  years,  H-.M.  disease  11  years  ago  Monkeys  injected 

(r)    Baby  at  the  breast,  brother  of  case  (a),  who  suffered  from  j    on  Aprils,  l9 I0- 
an  atypical  poliomyelitis  of  the  abortive  variety  J 

Result. — Control  monkey  (mixture  of  virus  with  normal  serum),  para- 
lysed in  seventeen  days,  died  on  April  23. 

Monkeys  injected  with  virus  and  serum  of  cases  (a)  and  (c)  remained 
well. 

The  monkey  injected  with  virus  mixed  with  serum  of  case  (b)  had 
paralysis  limited  to  the  left  hind  limb  and  survived. 

Xetter  and  Levaditi  draw  the  conclusion  that  antibodies  are  still 
present,  but  in  diminished  quantity,  after  eleven  years.  These 
observations,  together  with  our  own  experiment  2  (b)  throw  much 
light  on  the  question  of  duration  of  immunity  discussed  above. 

The  investigation  of  Xetter  and  Levaditi  of  case  (c)  shows  that 
specific  antibodies  are  formed  in  abortive  poliomyelitis.  Miiller  and 
I  were  able  to  bring  further  evidence  on  this  point. 

On  May  31,  1910,  the  following  monkeys  received  intracerebral  injections 
of  a  mixture  of  virus  and  serum  :  — 

(a)  Control  monkey  No.  58  (Macacus  rhesus).  A  mixture  of  virus  and 
serum  from  a  normal  new-born  child. 

June  1-10. — No  symptoms. 

June  11. — Paralysed. 

June  13. — Death  (see  p.  77). 

(b)  Monkey  No.  57  (Macacus  rhesus). — Mixture  of  virus  and  serum  of 
the  patient,  Erna  B. 

Result  of  the  inoculation. — Remained  permanently  well. 
Erna  B.  was  a  child  2  years  old,  who  suffered  from  a  rudimentary  form 
of  poliomyelitis. 

The  fact  that  antibodies  are  formed  even  when  the  poliomyelitis 
is  abortive  is  of  great  practical  importance.  In  our  own  case,  for 
example,  the  result  of  the  test  made  the  diagnosis  certain,  which 
it  was  not  before  the  test  was  made.  Anderson  and  Frost  were 
able  to  prove  that  atypical  poliomyelitis  was  present  in  six  doubtful 
cases  in  the  same  manner.  It  is  impossible  to  estimate  the  value 
of  serum  diagnosis  in  future  epidemics.  In  particular,  it  will  be 
necessary  to  find  out  if  antibodies  are  present  in  the  blood  serum  of 
people  who  live  with  the  sufferer  from  poliomyelitis,  but  who  are 
unaffected.  In  this  way  many  obscure  points  in  the  epidemiology 
of  the  disease  may  be  made  clear. 


170  EPIDEMIC   INFANTILE   PARALYSIS 

In  other  cases  a  negative  result  may  be  of  value,  as  in  the 
following  instance.  The  patient,  Daniel  Sell.,  aged  7,  and  three  of 
his  brothers  and  sisters  suffered  from  the  same  symptoms,  cough, 
vomiting,  and  diarrhoea,  without  any  neurological  symptoms.  The 
diagnosis  was:  Neuritis  and  acute  bronchitis;  the  suspicion  of 
poliomyelitis  cannot  be  excluded. 

The  mixture  of  the  patient's  serum  and  virus  No.  11  was  made  in  the 
usual  way  and  given  to  monkey  No.  61  (Macacus  rhesus)  by  intracerebral 
injection. 

June  14-17. — Well. 

June   18. — Paralysed. 

June  10. — Death.      (Details,  see  p.   52.) 

In  this  case  the  negative  result  of  the  test  enabled  poliomyelitis 
to  be  excluded;  the  diagnosis  was  not  very  probable  because  the 
patient  came  from  a  village  in  which  there  were  no  cases  of  polio- 
myelitis. 

Clinical  and  epidemiological  investigation,  particularly  by 
Medin,  has  shown  that  Strurnpell's  old  theory  was  correct,  namely, 
that  there  are  cerebral  forms  of  Heine-Medin  disease.  But 
undoubtedly  there  are  also  polio-encephalitic  processes  which  are  not 
connected  etiologically  with  Heine-Medin  disease.  In  such  cases 
serum  diagnosis  may  be  of  much  value.  The  following  serves  as 
an  example  of  this  :  — 

On  July  13,  iqio,  the  following  monkeys  received  intracerebral 
injections  :  — 

(a)  Control  monkey  No.  102  (Macacus  rhesus). — A  mixture  of  virus  and 
saline. 

Death  from  paralysis  on  July  26.      (See  Experiment  2,  p.   161.) 

(b)  Monkey  No.  65  (Macacus  rhesus). — A  mixture  of  virus  and  the 
serum  of  George  K. 

The  result  of  the  injection  on  July  13. — Monkey  No.  65  remained  per- 
manently well. 

Short  abstract  of  the  clinical  history  of  George  K. — Age  33  years,  had 
infantile  paralysis  during  the  first  year  of  life,  otherwise  no  important 
illness. 

Condition  on  June  28,  1910. — Internal  organs  normal.  Reflexes  all  brisk 
except  the  pupil  reflexes.  Patient  appears  mentally  dull.  Speech  is  slow 
and  stammering.  Comprehension  fairly  good.  The  whole  of  the  muscu- 
lature on  the  right  side  is  weaker  than  on  the  left  (leg,  arm,  face). 

Diagnosis. — Long-standing  cerebral  infantile  paralysis. 

In  this  case,  therefore,  proof  was  brought  forward  by  means 
of  serum  diagnosis  that  the  cerebral  form  of  infantile  paralysis  is 
identical  from  the  etiological  point  of  view  with  the  typical  spinal 
form  of  the  disease.  Further,  in  this  case  antibodies  were  present 
in  the  blood  of  a  patient  thirty-two  years  after  he  had  suffered  from 
the  acute  attack. 

A  number  of  authors  have  maintained  that  the  etiology  of 
herpes    zoster    is    the    same    as    that    of    poliomyelitis.     In    herpes 


THE     FIGHT     AGAINST    THE     DISEASE  171 

zoster  infiltration  of  the  intervertebral  ganglia  is  found,  which  is 
similar  to  infiltration  of  these  ganglia  found  in  spontaneous  and 
experimental  poliomyelitis  by  Swedish  and  American  authors 
(Forssner  and  Sj avail,  Strauss,  Flexner).  We  have  therefore 
examined  some  cases  of  herpes  zoster. 

On  June  13,   1910,  the  following  received  intracerebral  injections  :  — 

(a)  Control  monkey  No.  59  (Macacus  rhesus). — A  mixture  of  virus  No. 
1 1  with  serum  from  a  new-born  child. 

June  15-21. — Well. 

June  22. — Gastro-intestinal  symptoms. 

June  24. — Paralysis. 

Gradual  improvement.      (Details,  see  p.   56.) 

(b)  Monkey  No.  60  (Macacus  rhesus). — A  mixture  of  virus  No.  11  with 
serum  of  the  patient,  Adam  St. 

Result  of  the  infection. — Monkey  No.  60  remained  permanently  well. 

Short  abstract  of  the  clinical  history  of  the  patient,  Adam  St.,  farmer. — 
Some  days  ago  he  had  feelings  of  cold,  pains  in  the  knees,  and  swelling  of 
the  glands  in  the  inguinal  region ;  next  day  a  red  rash  on  the  left  thigh. 
Anorexia ;  furred  tongue.  Otherwise  no  symptoms.  Vesicular  eruption 
over  a  saddle-shaped  area  on  the  buttocks. 

Diagnosis. — Herpes  zoster. 

We  have  examined  two  other  patients  with  herpes  zoster  by 
this  method.  Both  monkeys  which  were  injected  with  a  mixture 
of  virus  and  serum  in  the  usual  way  remained  well  (Nos.  104  and 
105).  This  did  not  amount  to  proof,  because  unfortunately  the 
control  monkey  did  not  become  ill  either  (injected  with  a  mixture 
of  virus  and  serum  from  a  normal  new-born  child).  Possibly  this 
monkey  was  one  of  the  few  (5  per  cent.)  which  are  refractory. 
We  therefore  cannot  lay  much  stress  on  this  experiment,  although 
the  results  are  of  interest,  and  the  subject  must  be  investigated 
more  fully. 

WTe  are  convinced  that  this  method  will  prove  of  use  in  many 
other  doubtful  conditions,  e.g.,  in  some  cases  of  facial  palsy. 
Further,  it  may  be  applied  in  order  to  determine  whether  the  cases 
of  poliomyelitis  which  occur  with  measles  and  scarlet  fever  are 
cases  of  true  Heine-Medin  disease;  whether  they  are  due  to  acci- 
dental double  infection,  or  whether  there  is  some  other  etiological 
factor  at  work.  In  the  differential  diagnosis  of  poliomyelitis  and 
cerebrospinal  meningitis  the  serum  test  will  be  of  the  greatest  value. 

The  clinician  can  call  to  mind  many  other  conditions  which  are, 
as  yet,  little  understood.  We  are  only  at  the  beginning  of  such 
investigations,  and  the  preceding  research  is  meant  chiefly  to  indicate 
the  importance  of  such  investigation  and  the  methods  by  which  it 
may  be  carried  out. 

Serum  Therapy. — It  would  be  still  more  gratifying  if  the  anti- 
bodies could  be  made  use  of  in  therapeutics  as  well  as  for  purposes 
of  diagnosis.  Experience  with  the  virus  of  rabies  does  not  seem 
to  hold  out  much  hope  in  this  direction;  Kraus  has  shown  that 
although   the   antibodies   of  this   disease   prove   very   efficacious    in 


I72  EPIDEMIC   INFANTILE  PARALYSIS 

vitro  they  have  no  therapeutic  effect  either  as  a  preventive  or  a 
curative  measure.  On  the  other  hand,  Heine-Medin  disease  in  man 
runs  a  much  more  benign  course  than  rabies.  The  lack  of  any  other 
means  of  treating  the  disease  during  the  acute  stage  is  an  argument 
in  favour  of  trying  the  effect  of  treatment  with  antibodies.  I  have 
no  experience  in  this  matter;  my  experiments  came  to  an  end  owing 
to  lack  of  material  just  when  I  had  reached  the  stage  of  investiga- 
tion of  the  therapeutic  action  of  the  serum. 

Leiner  and  v.  Wiesner  gave  monkeys  simultaneously  intra- 
cerebral injections  of  virus  and  intraperitoneal  injections  of  large 
quantities  of  serum  containing  antibodies.  The  monkeys  so  treated 
became  paralysed  quite  as  quickly  and  as  severely  as  the  controls. 
Subcutaneous  and  intraspinal  injection  of  the  serum  also  proved 
useless. 

Levaditi  and  Landsteiner  had  similar  negative  results  :  — 

Monkeys  No.  79  (Mangabey)  and  No.  80  [Callitrichus)  were  infected  on 
January  19,  1910.  Monkey  No.  79  received  on  January  19,  20,  and  24  5  c.c, 
10  c.c,  and  5  c.c.  of  the  serum  of  a  monkey  which  had  survived  an  attack  of 
poliomyelitis.  Both  monkeys  became  paralysed  in  five  days.  Simultaneous 
intraspinal  injection  of  serum  and  intracerebral  infection  also  proved  useless. 

Monkeys  Nos.  92  and  93  [Rhesus)  were  given  intracerebral  infection  on 
February   12,    1910. 

Monkey  No.  92  received  2  c.c.  of  the  serum  of  a  highly  immunized 
monkey  into  the  theca  on  February  12,  13,  and  15.  Monkey  No.  92,  together 
with  the  control  monkey,  became  paralysed  on  February  17. 

Intraperitoneal  and  intraspinal  injections  of  the  serum  thus 
proved  to  be  of  no  curative  value.  Kraus  found  that  his  specifically 
active  sheep  serum  had  no  prophylactic  effect  (see  p.  166). 

The  outlook  for  serum  therapy  does  not  seem  bright.  Flexner 
and  Lewis  are  the  only  authors  who  have  obtained  any  positive 
results.  It  is  true  that  serum  injected  into  the  theca  had  no  effect 
on  monkeys  which  had  been  infected  by  intracerebral  injection,  even 
when  treatment  was  begun  very  shortly  after  infection.  But  when 
the  monkeys  were  infected  in  a  way  more  approaching  the  natural 
method,  according  to  these  authors,  the  serum  was  found  to  exert 
a  definite  influence  on  the  course  of  the  disease.  Monkeys  were 
infected  through  the  scarified  mucous  membrane  of  the  throat,  and 
were  given  repeated  intraspinal  injections  of  serum,  beginning  not 
later  than  twenty-four  hours  after  infection;  in  these  animals  the 
incubation  period  of  the  disease  was  found  to  be  as  long  as  twenty- 
six  days,  while  the  control  monkeys  became  paralysed  in  from  nine 
to  eleven  days.  Flexner  and  Lewis  suggest  that  if  treatment  had 
been  carried  on  longer  the  occurrence  of  paralysis  might  have  been 
prevented. 

They  obtained  these  results  not  only  with  the  serum  of  monkeys 
which  had  survived  the  disease,  but  also  with  serum  from  monkeys 
which  had  been  artificially  immunized  and  from  human  beings  who 
had  suffered  from  the  disease.       They  hope  to  raise  the  antibody 


THE    FIGHT     AGAINST     THE    DISEASE  1 73 

content  of  the  serum  by  specific  treatment  and  thus  to  provide  a 
serum  of  therapeutic  value.  They  consider  that  Heine-Aledin 
disease  produced  artificially  in  monkeys  is  a  much  more  serious 
disease  than  that  occurring  naturally  in  man.  On  the  other  hand,, 
we  must  remember  that  we  are  not  in  a  position  to  use  the  serum 
so  early  in  the  disease  in  man  as  Flexner  and  Lewis  were  able  to  in 
monkeys. 

The  only  experiment  carried  out  with  human  serum  in  man,  as 
far  as  I  know,  was  performed  by  Xobecourt  and  Darre.  They  gave 
an  intraspinal  injection  of  the  serum,  and  state  that  symptoms  of 
marked  meningeal  irritation  set  in  three  hours  after  the  injection 
and  continued  for  several  days,  but  that  no  definite  effect  on  the 
course  of  the  paralysis  could  be  observed.  Considering  how  extra- 
ordinarily variable  the  course  of  the  disease  is,  and  how  impossible 
it  is  to  give  a  prognosis  from  the  symptoms  of  the  prodromal  stage, 
it  is  evident  that  the  value  of  serum  therapy  can  be  established  only 
by  means  of  a  very  large  collection  of  statistics.  At  present  the 
question  is  still  in  the  experimental  stage. 

[Xetter,  Gendron,  and  Touraine  report  that  the  administration 
of  serum  from  an  old  case  of  poliomyelitis  into  four  acute  cases 
resulted  in  improvement  of  three  and  the  death  of  one  case. — 
Translator.] 

III.— EXPERIMENTS  WITH  DRUGS. 

Fermi  stated  that  the  course  of  rabies,  produced  artificially  in 
rabbits,  was  influenced  in  a  favourable  way  by  certain  dyes,  particu- 
larly by  Trypan  red.  I  therefore  made  some  experiments  on 
monkeys  with  this  substance,  but  they  were  quite  unsuccessful. 

Landsteiner  and  Levaditi  used  other  substances,  firstly 
arsacetin :  — 

Two  Macacus  monkeys  received,  on  the  same  day  and  in  the  same 
manner,  intracerebral  and  intraperitoneal  injections.  The  control  became 
ill  in  seven  days,  and  paralysed  in  eight.  The  other  monkey  was  given 
subcutaneous  injections  of  from  '075  to  '2  gr.  arsacetin  on  the  third, 
fifth,  and  sixth  days  after  infection.  It  became  ill  on  the  seventh  day  and 
paralysed  on  the  eighth. 

In  a  similar  way  they  used  arsenophenylglycin. 

Two  Macacus  monkeys  were  infected  in  the  same  way  as  in  the  preceding 
experiment.  The  control  became  paralysed  in  twelve  days.  The  other 
monkey  received  a  subcutaneous  injection  of  '3  gr.  arsenophenylglycin  at 
the  same  time  as  it  was  infected.  It  became  ill  six  days  afterwards,  and  was 
completely  paralysed  in  seven  days. 

Radium  and  X-rays  proved  equally  useless  both  for  prevention 
and  cure. 

Flexner  and  Clark  recently  turned  their  attention  towards 
urotropin.     Cushing  and  Crowe  have  shown  that  urotropin  injected 


174  EPIDEMIC  INFANTILE  PARALYSIS 

subcutaneously  passes  to  the  cerebrospinal  fluid,  and  they  have  used 
this  drug  as  a  prophylactic  antiseptic  in  their  operations  on  the  brain 
and  spinal  cord.  Moris  in  Baltimore  is  said  to  have  used  urotropin 
with  success  in  poliomyelitis.  Flexner  and  Clark  therefore  used 
this  drug  in  the  case  of  monkeys.  The  animals  took  it  well,  and 
it  appeared  in  the  cerebrospinal  fluid.  These  authors  infected 
monkeys  which  had  been  treated  with  urotropin,  and  they  continued 
the  treatment.  In  some  cases  the  period  of  incubation  was  pro- 
longed to  twenty-four  days,  instead  of  the  usual  six  to  eight  days. 
They  hope  to  achieve  better  results  by  combining  serum  treatment 
with  the  administration  of  urotropin. 

In  any  case,  these  American  experiments  show  that  a  certain 
amount  of  therapeutic  effect  can  be  produced  on  acute  poliomyelitis. 
So  far,  the  experiments  have  only  been  carried  out  in  animals  and 
have  been  protective,  and  not  curative,  in  character.  Both  serum 
and  urotropin  had  no  effect  on  poliomyelitis  in  monkeys  when  the 
disease  had  once  begun.  In  the  absence  of  any  known  method  of 
combating  the  disease  they  deserve  consideration. 

Other  therapeutic  measures  are  purely  symptomatic  and  it  must 
be  left  to  the  clinician  to  judge  of  their  usefulness  (rest,  careful 
nursing,  plaster  jacket  (Hohmann),  even  a  plaster  of  Paris  bed 
(Machol),  sodium  salicylate,  antipyrin,  aspirin,  phenacetin,  &c). 
Lumbar  puncture  appears  to  me  to  be  a  rational  method  of  treat- 
ment, because  I  have  found  increase  of  fluid  sometimes  in  monkeys. 

It  is  not  within  my  province  to  judge  of  the  purely  physical 
methods  necessary  during  the  period  of  convalescence  (baths,  active 
and  passive  movements,  electrical  treatment,  &c),  which  are  all 
directed  towards  the  prevention  of  contractures,  nor  of  the  ortho- 
paedic treatment  which  may  become  necessary  at  a  later  stage. 

IV. —PROPHYLAXIS. 

The  methods  to  be  adopted  for  prophylaxis  against  the  disease 
are  all  the  more  important  because  we  possess  no  means  of  in- 
fluencing the  disease  when  once  started.  We  are  driven  to  adopt 
special  measures  against  infantile  paralysis,  not  only  by  humane 
reasons,  caused  by  the  miserable  spectacle  of  the  paralysed  children 
themselves,  but  also  by  purely  economic  considerations.  As  Eduard 
Muller  says,  the  disease  is  more  to  be  feared  than  many  other 
infectious  diseases  of  childhood,  because  the  majority  of  those  who 
survive  remain  paralysed;  their  wage-earning  capacity  is  diminished 
or  destroyed,  and  they  remain  chronic  invalids.  Heine-Medin 
disease  produces  a  large  number  of  persons  who  are  physically  unfit 
and  are  a  burden  to  the  State.  Although  the  truth  of  this  is  obvious, 
it  seems  to  me  necessary  to  write  it,  because  I  have  heard  even 
physicians  say,  that  the  small  number  of  persons  affected  by  the 
disease  does  not  justify  any  special  measures.  It  is  true  that  so 
far  we  have  not  been  visited  by  an  epidemic  on  the  same  scale  as 
those  in  Norway  and  Sweden,  but  this  may  happen  at  any  time. 


THE    FIGHT     AGAINST    THE     DISEASE  175 

Even  from  the  humane  standpoint  alone,  it  is  our  duty  to  take 
measures  for  an  efficient  prophylaxis.  The  feeling,  often  expressed 
by  mothers  during  our  own  small  epidemic,  that  they  would  rather 
that  their  children  should  suffer  from  a  disease  more  dangerous  to 
life  than  from  infantile  paralysis,  is  based  on  a  very  sure  and 
instinctive  appreciation  of  the  consequences. 

In  the  face  of  the  recognized  necessity  for  efficient  prophylaxis, 
it  is  particularly  painful  to  have  to  realize  how  little  we  know  of 
the  usefulness  of  the  measures  proposed,  and  how  difficult  it  is  to 
carry  them  out.  The  following  suggestions  are  put  forward  with 
full  knowledge  that  they  are  not  in  any  sense  final,  and  that  they 
will  need  revision  and  correction  when  more  is  known  of  the  nature 
and  mode  of  occurrence  of  the  disease. 

Private  Prophylaxis. — It  will  be  useful  to  distinguish  between 
the  advice  which  may  be  given  by  the  private  practitioner  and  the 
measures  which  may  be  taken  by  the  State.  Both  must  depend 
upon  the  result  of  studies  in  the  epidemiology  and  pathogeny  of 
the  disease.  Wickman  has  proved  that  the  disease  is  transmitted 
from  one  human  being  to  another;  consequently  all  contact  with 
persons  who  may  be  carriers  of  the  virus  should  be  avoided.  The 
patient  should  be  isolated,  and  he  should  be  looked  after  by  only 
one  person,  if  possible.  This  will  not  be  enough  to  stop  all  possi- 
bility of  further  infection.  We  know  from  experience  that  in 
epidemics  the  virus  is  transmitted  more  frequently  by  persons 
suffering  from  the  slight,  abortive  type  of  the  disease,  or  by  healthy 
carriers,  than  by  the  patient  himself.  Isolation  of  the  patient  must 
not  be  omitted  on  this  account,  because  he  may  at  any  time  become 
the  source  of  spread  of  infection,  but  it  is  impossible  to  isolate  all 
the  persons  around  him.  We  possess  no  practicable  method  of 
separating  those  who  are  infected  from  those  who  are  not.  The 
method  of  serum  diagnosis  cannot  be  used  extensively,  because  it 
would  be  too  costly  and  because  the  result  of  the  test  would  be 
known  too  late  to  be  of  any  use.  All  we  can  do  is  to  warn  those 
who  have  been  in  contact  with  the  patient  that  they  may  carry 
the  infection  to  other  people,  and  to  advise  them  to  avoid  all  com- 
munication as  far  as  possible.  For  how  long  this  should  be  done 
I  shall  discuss  later.     Unfortunately  such  advice  is  rarely  followed. 

Careful  cleansing  of  the  mouth  is  clearly  of  importance,  when 
we  consider  that  the  virus  gains  entrance  in  all  probability  through 
the  mucous  membrane  of  the  mouth,  throat,  and  alimentary  canal. 
For  this  purpose  I  advise  the  use  of  a  i  per  cent,  solution  of  per- 
hydrol  because  of  its  disinfectant  action  on  the  virus  of  polio- 
myelitis (cf.  Chapter  III).  The  mechanical  cleansing  effect  of  this 
preparation  is  of  great  use  because,  during  the  act  of  gargling  or 
rinsing  the  mouth,  the  contact  between  the  virus  and  the  drug  is 
necessarily  short.  Preparations  of  menthol  have  a  destructive  effect 
upon  the  virus,  but  thymol,  which  is  much  used  as  a  mouth-wash, 
has  no  effect.  In  all  these  measures  any  excessively  active  use 
should  be  avoided,   in  order  that  the  mucous  membrane  may  not 


I  76  EPIDEMIC  INFANTILE  PARALYSIS 

be  damaged.  Experimental  experience  shows  that  the  presence  of 
any  lesion  of  the  mucous  membrane  renders  the  entrance  of  the 
virus  much  more  easy. 

In  this  connection  I  may  refer  once  again  to  the  greater  in- 
cidence of  the  disease  during  the  first  two  years  of  life.  It  is 
possible  that  there  is  a  germ  of  truth  in  the  idea  of  the  older 
English  physicians,  which  Heine  adopted,  that  troubles  of  dentition 
have  some  etiological  significance;  there  is  no  doubt  that  lesions 
of  the  mucous  membrane  are  very  frequently  present  at  that  age. 
The  greater  permeability  of  the  mucous  membranes,  which  is 
physiological  in  infants,  must  not  be  forgotten.  Such  measures  as 
are  taken  to  prevent  entry  of  the  virus  from  the  alimentary  tract 
are  all  based  upon  the  avoidance  of  lesions  of  the  mucous  membrane. 
Errors  in  diet  should  be  avoided.  Articles  of  food  do  not  convey 
the  infection,  nor  can  water  be  blamed.  Milk  from  an  infected 
house  may  be  contaminated  (Wickman),  but  milk  is  usually  boiled 
before  it  is  taken  nowadays.  Xervous  persons  may  be  reassured  by 
telling  them  that  a  temperature  of  6o°  is  sufficient  to  destroy  the 
virus. 

In  making  further  regulations  to  prevent  the  spread  of  infection 
from  the  patient  or  from  people  in  contact  with  him,  we  must  use 
our  experience  in  connection  with  the  excretion  of  the  virus.  Un- 
fortunately our  knowledge  is  still  limited  in  this  respect.  Experi- 
ments with  monkeys  have  shown  that  virus  is  found  in  the  nasal 
mucous  membrane,  but  it  has  never  been  demonstrated  in  the  nasal 
secretion.  As  we  have  no  definite  knowledge  it  would  be  wiser  to  do 
too  much  rather  than  too  little.  When  asked,  I  always  advise  the 
patient  and  all  persons  who  come  in  contact  with  him  in  any  way 
to  cleanse  the  mouth  and  throat  with  the  utmost  care,  because  of 
eventual  spread  of  the  disease  by  the  secretion. 

How  long  the  patient  and  the  "  carriers  "  remain  infectious  it 
is  impossible  to  say. 

Osgood  and  Lucus  found' virus  in  the  mucous  membrane  of  the  throat  in 
monkeys  six  months  after  intracerebral  injection.  At  that  time  they  were 
able  to  show  that  virus  had  already  disappeared  from  the  central  nervous 
system.  If  this  is  also  correct  for  human  beings  it  explains  many  "  sporadic  " 
cases,  but  it  emphasizes  the  necessity  for  disinfection  of  the  mouth  as  a 
prophylactic  measure. 

Medical  men  should  practise  the  most  careful  prophylaxis,  they 
are  peculiarly  liable  to  act  as  carriers  of  the  virus.  It  is  advisable 
to  disinfect  the  faeces,  vomit,  and  urine  of  the  patient.  A  2  per 
cent,  solution  of  potassium  permanganate  destroys  the  virus,  and 
solutions  of  a  high  degree  of  concentration  will  disinfect  the  dejecta. 
The  underlinen  and  bedclothes,  and  particularly  the- pocket  handker- 
chiefs, of  the  patient  must  be  disinfected;  ordinary  boiling  in  the 
wash  is  sufficient  owing  to  the  peculiar  sensitiveness  to  heat  of  the 
virus.     The  foregoing  measures  must  be  used  also  by  the  nurse. 

It  has  been  found  that  the  house  in  which  cases  of  poliomyelitis 


THE    FIGHT     AGAINST     THE     DISEASE  177 

have  lived  may  retain  the  infection.  In  most  instances  in  which 
this  is  said  to  have  happened  it  is  probable  that  the  virus  was 
conveyed  by  direct  contact  with  a  human  being".  However,  the 
possibility  cannot  be  excluded  that  virus  was  given  off  in  some 
secretion  or  excretion  from  the  patient  and  remained  active  owing 
to  its  powers  of  resistance.  Wickman  brought  forward  some 
evidence  in  support  of  this  view.  It  is  therefore  advisable  to  carry 
out  a  disinfection  of  the  house.  We  have  tested  the  value  of 
formalin  for  this  purpose. 

The  experiment  was  carried  out  in  the  usual  way  by  means  of  Flugge's 
Breslau  apparatus.  The  dimensions  of  the  room  chosen  were  4/93  x  3*4  X3"84 
metres.  The  formalin  and  water  necessary  were  calculated  according  to 
Flugge's  tables.  The  poliomyelitis  virus  was  exposed  in  the  middle  of  the 
room  in  an  open  Petri  dish ;  it  was  obtained  by  drying  the  spinal  cord  of  a 
monkey  suffering  from  poliomyelitis  in  vacuo  and  rubbing  it  down  in  a 
mortar.  Silk  threads  covered  with  the  spores  of  anthrax  were  placed  close 
to  the  dish  as  a  control.  The  formaldehyde  was  allowed  to  act  for  seven 
and  a  half  hours.  Culture  tubes  inoculated  with  the  anthrax  spores  which 
had  been  exposed  to  the  formalin  vapour  showed  no  signs  of  growth  in  thirty 
days.  Tubes  inoculated  from  threads  which  had  not  been  thus  exposed 
showed  definite  growth  in  twenty-four  hours.  Monkey  No.  35  was  given  an 
intracerebral  injection  of  '5  c.c.  of  a  5  per  cent,  emulsion  of  the  spinal  cord 
exposed  to  the  formalin.  At  the  same  time  monkey  No.  36  received  '5  c.c.  of 
a  5  per  cent,  emulsion  of  the  spinal  cord  not  so  exposed.  Monkey  No.  36 
become  paralysed  after  fourteen  days,  and  died  on  the  seventeenth  day  after 
injection.     Monkey  No.  35  remained  well  permanently. 

The  usual  disinfection  with  formalin  is  therefore  sufficient  to 
destroy  the  virus  under  these  conditions.  It  is  to  be  supposed  that 
other  modern  methods  of  disinfecting  rooms,  when  carried  out  in 
the  same  energetic  way,  will  prove  equally  efficacious. 

State  Regulation. — It  remains  to  be  seen  in  what  way  pro- 
phylaxis may  be  furthered  by  the  State.  I  believe  that  notification 
is  of  the  first  importance ;  Eduard  Midler  also  agrees  with  me  that  it 
should  be  carried  out  not  only  in  times  of  epidemic,  but  always. 
Quite  apart  from  the  usefulness  of  this  measure  in  making  known 
the  number  of  sporadic  cases  which  occur,  and  thus  keeping  the 
disease  before  the  minds  of  practitioners  even  when  there  is  no 
epidemic,  it  will  enable  us  to  take  steps  immediately  a  case  occurs 
and  even  prevent  the  development  of  an  epidemic  by  prophylactic 
means  in  some  instances.  It  is  very  much  to  be  hoped  that  some 
reliable  method  of  early  diagnosis  will  be  discovered.  Flexner's 
proposal,  that  lumbar  puncture  should  be  used  early  for  diagnostic 
purposes,  should  be  more  widely  followed.  In  one  case  Flexner 
was  able  to  assist  materially  towards  a  diagnosis  by  discovering 
an  increase  in  the  quantity  of  albumin  present  and  an  absence  of 
bacteria. 

For  the  rest,  we  shall  do  well  to  proceed  cautiously  in  intro- 
ducing any  further  State  regulation  of  the  disease.  Compulsory 
isolation  is  not  justifiable  in  the  present  state   of  our  knowledge. 

12 


iyg  EPIDEMIC  INFANTILE  PARALYSIS 

For  the  same  reason  I  do  not  think  it  necessary  that  the  public 
should  be  alarmed  by  the  introduction  of  compulsory  disinfection 
of  clothes,  household  linen,  and  of  rooms.  Muller  rightly  draws 
attention  to  the  damage  to  property  which  this  entails,  and  to  the 
loss  which  results  from  declaring  a  place  of  business  to  be  infec- 
tious. Although  we  can  ignore  such  considerations  when  dealing 
with  the  subject  from  the  purely  hygienic  standpoint,  yet  from  the 
practical  point  of  view  they  are  of  very  considerable  importance. 
On  the  other  hand,  the  physician  in  charge  of  a  case  may  do  much 
by  impressing  on  the  relatives,  in  a  tactful  way,  the  importance 
of  simple,  practicable  prophylactic  measures.  The  uniformed 
inspector,  carrying  out  these  proceedings  in  as  conspicuous  a  way 
as  possible,  is  not  a  sight  we  should  wish  to  see. 

In  another  direction  the  sanitary  authorities  may  well  take 
action.  The  brothers  and  sisters  of  children  suffering  from  the 
disease  should  be  forbidden  to  attend  school  for  a  period  of  some 
weeks  (unfortunately  we  cannot  say  exactly  for  how  long).  In 
times  of  epidemic  the  schools  should  be  closed.  The  objection  has 
been  raised  to  this,  that  the  children  meet  at  play  if  they  are  not  at 
school.  I  do  not  think  that  this  is  relevant,  because  it  is  well 
known  that  children  from  all  parts  of  the  town  do  not  flock  to  one 
place  to  play,  as  they  do  in  the  case  of  the  school.  Wickman's 
experience  at  Trastena  has  proved  how  the  school  favours  the 
spread  of  infection.  During  epidemics  children  should  not  be 
allowed  to  attend  church  (Muller);  the  evil  practice  of  permitting 
children  to  attend  the  funerals  of  comrades  who  have  died  of  Heine- 
Medin  disease  should  be  stopped;  on  such  occasions  contact  with  the 
house  and  with  the  relatives  is  usually  impossible  to  avoid.  Vac- 
cination should  not  be  performed  during  an  epidemic,  and  no 
children's  parties  should  be  given. 

It  is  the  duty  of  the  sanitary  authorities  to  give  full  information 
concerning  the  measures  which  are  considered  advisable  to  all 
doctors  in  some  suitable  form. 

This  represents  all  that  it  is  wise  to  do  at  the  present  time 
in  fighting  Heine-Medin  disease  along  hygienic  lines.  If  we  carry 
out  these  measures  we  shall  feel  at  least  that  we  have  done  our 
duty.  Only  practical  experience  can  tell  us  whether  thereby  we 
really  reach  the  virus. 

CONCLUSION. 

The  attempt  made  in  this  book  to  give  a  comprehensive  descrip- 
tion of  Heine-Medin  disease  shows  how  impossible  it  is  to  do  so, 
in  spite  of  the  many  remarkable  advances  which  have  been  made 
during  the  last  few  years.  The  study  of  poliomyelitis  provides  us 
with  another  example  of  the  manner  in  which  additions  to  our 
knowledge  make  us  conscious  of  further  and  further  regions  of  the 
unknown. 

The  clinical  aspect  of  the  problem  may  be  regarded  as  having 


THE    FIGHT     AGAINST     THE     DISEASE  179 

been  investigated  almost  in  its  entirety,  thanks  to  the  labours  of 
Heine,  Medin,  and  Wickman.  Observation  of  the  last  great 
epidemics  has  shown  that  there  is  not  much  more  to  be  discovered 
in  that  direction.  There  is  one  important  gap,  however,  which 
remains  to  be  filled  in,  the  discovery  of  a  certain  means  of  early 
diagnosis.  The  studies  of  Eduard  Miiller  show  that  progress  is 
possible  (he  lays  stress  on  the  heavy  perspiration,  the  hyperesthesia, 
and  the  leucopeniaj. 

From  the  pathological  point  of  view  the  study  of  the  disease 
is  complete,  except  in  so  far  as  refinements  of  microscopical  methods 
may  yield  fresh  discoveries.  In  spite  of  the  investigations  of 
Wickman,  and  in  spite  of  the  results  obtained  by  the  experimental 
method,  the  question  of  the  pathogenesis  of  the  disease  remains 
obscure  and  debatable  on  many  points.  Systematic  experiments 
with  animals  will  do  much  to  make  clear  this  part  of  the  subject. 

I  have  tried  to  emphasize  the  many  points  in  the  epidemiology 
of  the  disease  which  are  still  doubtful,  even  after  Wickman's 
researches.  We  will  not  hope  that  opportunities  will  arise  in  which 
we  shall  be  able  to  study  the  epidemiology  on  a  large  scale;  but 
we  may  hope  that,  if  our  fears  are  realized,  all  will  be  done  which 
is  possible  to  furnish  us  with  new  weapons  for  prophylaxis. 

The  main  object  of  this  book  was  to  bring  forward  proofs  that 
the  method  of  experiment  with  animals,  the  most  recent  branch  of 
research,  is  able  not  only  to  confirm  the  results  obtained  by  the 
older  methods  of  investigation,  but  also  to  throw  fresh  light  upon 
them  and  to  yield  new  results  in  its  turn.  If  the  reader  should 
feel  disappointed  that  the  actual  results  are  not  larger  and  more 
important  than  he  finds  them,  I  would  ask  him  to  consider  that 
this  method  is  still  young,  and  that  the  peculiar  characteristics  of 
the  only  animal  which  is  suitable  for  the  experiments  limit  the 
range  and  variety  of  the  investigations  very  strictly.  This  is  surely 
a  field  in  which  the  authorities  might  render  practical  assistance, 
in  order  that  the  therapeutics  of  this  pest — until  now  the  most 
obscure  chapter  in  poliomyelitis — may  come  to  be  understood. 
There  is  no  doubt  that  the  answer  to  many  unsolved  problems  will 
be  given  ultimately  by  experimental  research. 

May  the  experimental  study  of  Heine-Medin  disease  be  in  a 
position  to  fulfil  the  nobile  officium,  which  devolves  upon  it  from 
the  great  series  of  pioneers  named  in  the  first  chapter  of  this  book, 
who  have  brought  our  knowledge  to  its  present  pitch  by  other 
means.  The  study  of  their  works  recalls  to  one's  mind  the  com- 
parison made  by  Goethe,  by  which  he  used  to  express  the  sensation 
which  seized  him  while  studying  the  profound  writings  of  Kant. 
They  give  one  the  sensation  as  of  entering  a  brightly  illuminated 
room. 


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Jahrb.  f.  Kinderkrankh.,  36. 
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Jahrb.  d.  Psych,  u.  Neurol.,  31. 
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1 82  EPIDEMIC    INFANTILE    PARALYSIS 

Carles.  Sur  quelques  cas  de  paralysie  des  muscles  de  la  paroi  abdominale  au 
cours  de  la  poliomyelite  anterieure  aigue.  Gaz.  hebd.  des  Soc.  med. 
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Cassirer.  Uber  metastatische  Abscesse  im  Zentralnervensystem.  Arch.  f. 
Psychiatrie,  36,   1902. 

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Wochenschr.,  50,   1910. 
Catola.     A    proposito    di    un   caso    di    mielite    acuta    a  tipo    ascendente    con 

speciale   reperto  batteriologico.     Policlinico,   S.    M.,    iqii.    No.    1. 
Caverly.      History    of    an    epidemic    of    acute    disease    of    an    unusual    type. 

Med.    Record,    1894. 

—  Notes  of  an  epidemic  of  acute  anterior  poliomyelitis.     Journ.   of  Amer. 

Med.  Assoc,  26,   1896. 
Ceni.     La   formazioni   di   cavita  medollari   in   un   caso   di   poliomyelite   ant. 

acut.     Riv.   sper.   di  Fren.,  30,   1904. 
CESTAN.      Tremblement   hereditaire  et   atrophie   musculaire   tardive   chez  un 

malade    porteur   d'un    foyer    ancien    de    paralysie    infantile.      Progres 

med.,   1899. 
CESTAN   and  HUET.      Contribution   clinique   a   l'etude   de   la   topographie  des 

atrophies  musculaires  myelopathiques.       Nouv.    iconogr.   de   la   Salp., 

1902. 
Cestano-Savini  and   SAVINI.     Zur  Kenntniss  der  pathologischen  Anatomie 

und  der  Pathogenese  eines  unter  dem  Bilde  der  aufsteigenden  Landry- 

schen    Paralyse    verlaufenden    Falles  von    Poliomyelitis   beim   Kinde. 

Arch.  f.  Psych.,  1909. 
Chapin.     Epidemic   paralysis   in  children.     Journ.    of   Amer.    Med.    Assoc, 

Dec.   1,  1900. 
Charcot  and  JOFFROY.     Cas  de  paralysie  infantile  spinale  avec  lesions  des 

cornes  anterieures  de  la  moelle  epiniere.     Arch.    de.   phys.   normal  et 

pathol.,  3,   1871. 
CHARCOT,   S.   M.      Lee   sur  les  malad.   du  systeme  nerv.      Publ.   par  Bourne- 

ville,  2,  Second  edition.     Paris,  1877. 
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Assoc,  Aug.  3,  1912. 
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pupillaren  Symptomen.     Deutsche  med.   Wochenschr.,  38,   1905. 
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d.  norske  laegeforening,  1906.      N.F.,  Jahrg.  26,  p.  62. 
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poliomyelitie  aigue  de  Fadulte.     Compt.  rend,  de  la  Soc.  de  Biol.,  70, 

1911. 
COLLINS.      The  epidemiology  of  poliomyelitis.    Journ.  of  Amer.  Med.  Assoc, 

54,  24,  1910. 
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recent  epidemic  in  New  York  City.     Med.  Record,  74,  p.  248. 
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1843,  xxxi,  248. 
Concetti.     Rapport   sur   les   meningites   aigues   non   tuberculeuses   chez   les 

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Lyon  medicale,   1S88. 
CORNIL.     Paralysie  infantile.     Compt.  rend,  des  seances  et  mem.  de  la  Soc 

de  Biol.,  Nov.,   1863. 
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March  30,   1912. 
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— ■  Etude  critique  sur  les  rapports  de  la  meningite  cerebrospinal  et  de  la 

paralysie  infantile.     Journ  med.   franc. ,   1910. 


LITERATURE  1 83 

CURRIE  and  Bramwell.  A  local  epidemic  of  acute  poliomyelitis.  Rev.  of 
Xeurol.  and  Psych.,   191 1,  ix,  p.    10. 

DAHM.      Diskussionsbemerkungen     im     Duisberger    Arzte-Verein,     Xov.     26, 

1909.     Miinch.    med.    AA'ochenschr.,   49,    1909. 
Dauber.     Zur  Lehre  von  der  Pol.  ant.  acuta.     Deutsche  Zeitschr.  f.  Xerven- 

heilk.,  4,   1893. 
Davidsox.     Lancet,   Feb.,   191 1. 
DEJERIXE.      Xote      sur   deux   cas   de   paralvsie   infantile.     Le    Progres   med., 

1S78. 
DEJERLXE  and  HUET.      Contribution  a  l'etude   de   la   paralvsie  atrophique   de 

Fenfance  a  forme  hemiplegique.     Arch,   de  Physiol.,   1888. 
DEXECHAX  and   GROSGEORGES.      Une    epidemie     de     paralvsie     infantile     en 

Anjou.      Paris  med.,  April  22,  igii. 
DERCUM.     Journ.  of  Xerv.   and  Ment.   Dis.,   1900. 
DETHLOFF.      Om  poliomyelitismikroben    (Xogle  bemerkninger   ianledning  of 

Diskussionen     i    Medicinsk    selskab.     Kristiana).       Xorsk.     Mag.     for 

Laegevid.,   1906,  Xo.  3,  p.  361. 
DEUTSCHLAXDER.      Spinale    Kinderlahmung.      Deutsche     med.    AVochenschr., 

Xo.  40,   1912. 
Dixox,    FOX  and  Rucker.     Micro-organisms   found   in   the   blood   of   cases 

of  acute  poliomyelitis.      Pennsylvania  Board  of  Health,  191 1. 
Dixhexxe,  fils.     De  la  paralvsie  atrophique  graisseuse  de  l'enfance.    Arch. 

gener.   de  Med.,   1864,  July,  August,  October. 

—  De  Boulogne,  De  l'electrisation  localisee.     Paris,  1855  and  1870.     Third 

edition. 
DUPRE    and    Huet.      Paralvsie    spinale    infantile    localisee    aux    muscles    du 

groupe  radiculaire  superieure  de  plexus  brachial.     Rev.  neurol.,  1902. 
DUQTJENNOY.      Sur  une  forme  a  debut  douloureux  de  la  paralvsie  infantile. 

Diss.,  Lille,  1898. 
DUTIL  and  BALLET.      De  la  paralysie  ascendante  de  Landrv.      Semaine  med., 

1S95. 

ECKERT.      Uber     das     akute     Stadium     der     epidemischen     Kinderlahmung. 

Deutsche  med.   AVochenschr.,   3,   191 1. 
EDIXGER.       Vom     Bau     und     einigen     Erkrankungen     des     Xervensystems. 

Jahreskurse  f.  arztl.   Fortbildung,   1910,  Heft  5. 
Edwards.     Contribution  a  l'etude  de  la  paralysie  spinale  aigue  de  l'adulte 

et  de  sa  nature.      These  de  Paris,   1898. 
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Record,   X.Y.,    1891. 
ElCHELBERG.      Uber   spinale   Kinderlahmung.      Deutsche   med.    AA'ochenschr., 

3,   1910. 
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Schweitz.  Arzte,  10  July,   1910. 
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1879. 

—  Zur  pathologie   und   patholog.    Anatomie   der   spinalen   Kinderlahmung. 

Deutsch.  Arch.  f.  klin.  Med.,  26,  1880,  p.   557. 

—  Poliomyelitis  ant.   subacute  cervicalis  circumscripta  beim  Erwachsenen. 

Xeurol.    Zentralbl.,   i  Jahrg. ,    1S92,  p.   409. 
- —  Zur  Lehre  von  der  akuten  spinalen  Paralysie.     Arch.   f.   Psvchiatrie,   5, 

1875. 
ELLERMAXX.      Uber   den   Befund  von   Rhizopoden  bei  zwei   Fallen   von   Pol. 
ac.     Zentralbl.  f.  Bakt.,  40  (orig.),  Heft  5,  p.  648. 

—  Ej    eudommelige    Celler   i    Spinalvasken    ved    et    Tilfselde  af    Pol.    ac. 

Hosp.  Tid.,  1905,  47,  S.  1 134. 

F.XGEL,  FR.  Bakteriologischen  Ergebnis  einer  Lumbalpunktion  bei  Polio- 
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EXGLAXD,  F.  A  record  of  some  cases  of  epidemic  paralysis  occurring  in 
Hampshire.      Brit.   Med.  Journ.,  Dec.  3,   191 1. 

ERB,  AA~.  Uber  akute  Spinallahmung  bei  Erwachsenen  und  uber  verwandte 
spinale  Erkrankungen.  Arch.  f.  Psvch.  und  Xervenkrankh. ,  5,  1875^ 
p.   758.  "  . 

—  Uber    Modifikationen   der   partiellen    Entartungsreaktion    und  liber    das 

Vorkommen  der  chron.   atroph.   Spinallahmung  beim  Kinde.      XTeurol. 
Zentralbl.,  18S3,  Xo.  8,  p.   169. 


184  EPIDEMIC    INFANTILE    PARALYSIS 

ERB,  W.  Zur  Lehre  von  der  Unfallserkrankungen  des  Riickenmarks.  Uber 
Poliomyelitis  ant.  chron.  nach  Trauma.  Deutsche  Zeitschr.  f. 
Xervenheilk.,   11,  p.    122. 

—  Poliomyelitis  acuta  superior.     Deutsche  med.  Wochenschr.,   1906. 
ESHXER.     A  possible   second   attack   of   acute   anterior   poliomyelitis   in    the 

same  patient.     Med.  Record,  13,  1910. 

Farrar.      Outbreaks    of    disease    affecting-    the    cerebrospinal    system   in   the 

Midland   Counties    and    Dorsetshire    in    1910.      Report    to    L.G.B.    on 

Public  Health.     New  Series,  Xo.  61,  1912. 
Fetra.     Early    symptoms    in    sixty-three    cases    of    the    recent    epidemic    of 

Poliomyelitis.     Arch,  of  Ped._,  May,   1909. 
FLEXXER.      The     contribution     of     experimental     to     human     poliomyelitis. 

Journ.  of  Amer.  Med.  Assoc,  Sept.  24,  1910. 

—  The    control     of     epidemic    poliomyelitis.       Amer.     Journ.     of    Dis.     of 

Children,  August,  191 1,  2. 
— ■  Experimental  poliomyelitis.     Folia  Serologica,  vii,   191 1,  p.  1101. 
FLEXXER     and     CLARK.      Experimental    poliomyelitis     in     monkeys.     Journ. 
of  Amer.  Med.  Assoc,  56,  xo.  7,  Feb.   18,  1911. 

—  Experimental  poliomyelitis.      Ibid.,  Nov.    11,   191 1. 

—  Contamination  of  the  fly  with  poliomyelitis  virus.      Ibid.,  June  10,   191 1. 
Flexxer  and  LEWIS.     The  transmission  of  acute  poliomyelitis  to  monkeys. 

Journ.  Amer.  Med.  Assoc,  53,  1909;  20,  Nov.  13,  1909. 

—  The  transmission   of   acute   poliomyelitis   to   monkeys.      Ibid.,    53,    1909; 

23,  Dec.  4,  1909. 

—  The  nature  of  the  virus  of  epidemic  poliomyelitis.      Ibid.,   53,   1909;  25, 

Dec.   iS,  1909. 

—  Uber   experimentell    erzeugte    akute    Poliomyelitis    bei    Affen    und    die 

Xatur  ihres  Erregers.     Munch,  med.  AVochenschr.,  2,  1910. 

—  Epidemic    poliomyelitis    in    monkeys.     Journ.    of    Amer.    Med.    Assoc, 

Jan.    1,   1910. 

—  Epidemic  poliomyelitis  in  monkeys.     A  mode  of  spontaneous  infection. 

Ibid.,  Feb.   12,   1910. 

—  Experimental  epidemic  poliomyelitis  in  monkeys.      Ibid.,  April  2,  1910. 

—  Experimental    epidemic   poliomyelitis    in   monkeys.       Journ.    of    Experi- 

ment. Medic,  12,  2,  1910. 

—  Experimental    epidemic    poliomyelitis    in    monkeys.     Journ.     of    Amer. 

Med.  Assoc,  54,  Xo.  22. 

—  Experimental  epidemic  poliomyelitis  in  monkeys.      Ibid.,   55,   1910. 
Flexxer,    Peabody,    and    Draper.     Epidemic    poliomyelitis.     The    visceral 

lesions  of  a  human  case.     Journ.  of  Amer.  Med  Assoc,  Jan.   13,  1912. 

Foerster.  Ein  Fall  von  Poliomyelitis  im  obersten  Halsmark.  Allg.  med. 
Zentralzeitung,  1902. 

—  Zur     symptomatologie     der    Poliomyelitis    acuta     anterior.      Berl.  klin. 

Wochenschr.,  49,    1909. 
Forbes.     A  note  on  the  cerebrospinal  fluid  in  acute  poliomyelitis.     Lancet, 

18  Nov.,  1911. 
Forssxer  and  SjOVALL.     Uber  die  Poliomyelitis  acuta  samt  einem  Beitrag 

zur  Xeuronophagiefrage.      Zeitschr.   f.   klin.   Med.,    1907. 
FOX.      The     pathogenesis     of    poliomyelitis.      Zentralbl.     f.     Bakt.     Abt.     1, 

Ref.  49,  Heft,  20-21. 
Fraexkel,  A.     Demonstration  von  mikroskopischen  Praparaten  eines  Falles 

von  spinaler  Kinderlahmung.     Verein  f.  innere  Med.  in  Berlin,  Nov. 

19,  1906.     Deutsche  med.  Wochenschr.,  2,   1907. 
V.   Fraxkl-Hochwart.     Uber  die  gegenswartige  Poliomyelitis-Epidemie  in 

Wien.     Munch,   med  Wochenschr.,  49,   1908. 
Freedmax.     Acute    anterior    poliomyelitis.       Cleveland    Med.    Journ.,    1912, 

Xo.    9. 
FREY.      Uber  temporare  Lahmungen,  usw.       Berl.   klin.   AVochenschr.,    1874, 

:"3- 
FRIEDJUXG.      Zur  Kenntniss   der   Poliomyelitis  acuta   anterior.      AA  ien.    med. 

Wochenschr.,  39,   1909. 
FRIEDLAXDER.      tiber    A'erkalkung    der    Ganglionzellen.     ATrchow's    Archiv. 

88,  1882. 
Frissell.     Poliomyelitis  anterior  epidemica.     Journ.  of  Amer.  Med.  Assoc. 

Mar.  4,  191 1. 


LITERATURE  1 85 

FROST.  Conferences  on  epidemic  poliomyelitis  of  the  meeting  of  the 
American  Public  Health  Association.  Milwaukee,  Sep.,  igio.  Public 
Health  Reports,  1910,  41. 

—  The   field   of   investigation   of   epidemic   poliomyelitis.      Ibid.,    25,    1910, 

46. 
Ft'RXTRATT.      Uber  Poliomyelitisepidemien  mit  besonderer  Beriicksichtigung 
der  diesjahrigen   Epidemie   in  Steiermark.      Das   osterreiche   Sanitats- 
wesen,  Jahrg.  xxi,  igog;  Beil.  zu  Xo.  49,  p.  79. 

Garrow.     Brit.  Med.  Journ. ,  igio,  vol.  ii  (suppl.,  p.  393). 

GASTERS.     Vorlaiifige    Mitteilung   uber  anscheinend    epidemisches   Auftreten 

von    Poliomyelitis    anterior,    der    sog.    Heine-Medinschen    Krankheit. 

Zeitschr.  f.  Med.-Beamte,  17,  igog. 
GAUJOUX,   Emile  and  EUGEXE.      De  l'authenticite  des  epidemies  recentes  de 

paralysie  infantile.      Gaz.  des  hopit.,   191 1,  Xos.   5  and  6. 
VAX   GEHUCHTEN.      Pol.    on   Polynevrite.      Un   cas   de  paralysie   segmentaire. 

Annales  de  la  Soc.  beige  de  Xeurol.,  iSgg,  Xo.  6. 

—  La  poliomyelite  anterieure  aigue  de  l'adulte.     Arch,    de  Xeurol.,    1903, 

16,  p.  331- 

—  Cas  de  poliomyelite  anterieure  aigue  de  l'adulte.      X'evraxe,   1904. 
Geirsvold.       Epidemisk      (i  poliomyelit.,"      Bacteriologiske     undersogelsor. 

X'orsk  Mag.  for  Laegevid.,  Dez.,   1905,  S.    1280. 
GELMA.      Pari,    spin    infant.,    reprise    tardive    d"amyotrophie.      Rev.    neurol., 

igi2,  Xo.  3. 
GlBXEY    and    WALLACE.      The    recent    epidemic    of    poliomyelitis.     Journ.    of 

Amer.   Med.  Assoc,  4g,  1907,  25. 
Gilbert    and    Liox.     Les   paralysies    produites    par    le   bacille    d'Escherich. 

Compt.  rend,  de  la  Biol.,   i8g2. 
GIXS.      Ein   Beitrag  zur  Poliomyelitisfrage  nebst   Beschreibunf   eines  neuen 

fur  A'ersuch  am  Affen  geeigneten  Kafigs.     Zentralbl.  f.  Bakt.,  Abt.   1, 

59,  1911,  Heft  4. 
GlOSEFFl.      Die     spinale    Kinderlahmung     in    unserer    adnatischen     Region. 

Revista  di  clinica  pediatria,    191 1,  8. 
GOLDSCHEIDER.      Uber    Poliomyelitis    anterior.       Verein    f.    innere    Med.    zu 

Berlin,    Jan.    2,    1893;    Jan.    23,     1893;    Berl.    klm.    AVochenschr.,    16 
__  and  30,  1893. 
— ■  Uber  Poliomyelitis.     Zeitschr.  f.  klin.  Med.,  23,   1893. 
Goldscheider    and     Brasch.     Poliomyelitis.     Handb.     d.     path.     Anat.     d. 

Xervensystems.      Berlin,    1903. 
Gombault.      Xotes  sur  un  cas  de  paralysie  spin,  de  l'adulte  suivi  d'autopsie. 

Arch,   de  physiol.   norm,   et  pathol.,    1873. 
GOSSAGE.     The  etiology  of  infantile  paralysis.     Amer.   Journ.  of  Med.    Sc, 

1902,  p.  789. 
Gowers.     A  manual  of  diseases  of  the  nervous  system.     Second  edition,   1. 

London,  1892. 

—  A   case   of   anterior    poliomyelitis  and   multiple    neuritis.      The   Clinical 

Society's  Transactions,  iSg3. 

Grawitz.  Ein  Fall  von  Poliomyelitis  acuta  bei  einer  Erwachsenen.  Berl. 
klin.   Wochenschr.,    12,    i8g6. 

GREGOR  and  Hopper.  Clinical  observations  on  an  epidemic  of  acute  polio- 
myelitis in  Cornwall.  Proc.  Row  Soc.  Med.  (Clin.  Sec,  p.  28),  Nov., 
191 1.      Brit.   Med.   Journ.,   Xov.   4,   ign. 

GROBER.  Zu  der  rheinisch-westfalischen  Epidemie  von  spinaler  Kinder- 
lahmung.    Med.  Klin.  47,  igog. 

—  Die      akute      epidemische      Kinderlahmung.      Fortschritte      d.      deutsch. 

Klinik,   igio. 
GROSGEORGES.      La  poliomyelite  dans  l'An-jou.      These  de  Paris,    ign. 
GUTNON  and  RlST.    Deux  cas  de  poliomyelite  anterieure  aigue  sans  reaction 

meningee  cytologique  chez  un  frere  et  une  sceur.      Compt.  rend,   de  la 

soc.  des  hopit.  de  Paris,   1903. 
GUMPERTZ.      Uber    einen    ungewohnlichen    Fall    von    Poliomyelitis    ant.    ac. 
adult,    auf   infectioser    Grundlage.     Berl.    klin.    Wochenschr.,    16,    igoo. 

Hagexbach.     Uber     Poliomyelitisepidemien     in     der     Schweiz.     Korrespon- 

denzbl.  f.  Schweiz.  Arzte,  Jahrg.  40,  Heft  33-36. 
Harbitz,    F.      Poliomyelitis-Epidemien.     Tidskrift    f.    d.    orske    laegefore- 

ning.  N.F.,  igo6,  Jahrg.   16,  S.  82. 


1 86  EPIDEMIC    INFANTILE     PARALYSIS 

HARBITZ  and  Scheel.      Pathologisch-anatomische  Untersuchungen  uber  akute 
Poliomyelitis    und    verwandte    Krankheiten    von    den    Epidemien    in 
Norwegen  1Q03  bis  igo6.      Christiania,   1907. 
—  Akute     Poliomyelitis     und     verwandte     Krankheiten.     Pathologisch- 
anatomische   Untersuchungen   aus   den   Epidemien   in   Norwegen   1903 
bis  1906.     Deutsche  med.   Wochenschr.,  48,    1907. 
— ■  — ■  Epidemic   acute    Poliomyelitis    in    Norway    in    the   years    1903-1906. 
Journ.  of  Amer.  Med.  Assoc,  49,  1907,  No.   17. 
—  The  microbe  of  poliomyelitis.      Ibid.,  50,  1908,  4. 

HEIMANN.      Clinical  study  of  anterior  poliomyelitis.     Arch,   of  Ped.,   1909. 

Heine,  J.     Beobachtungen  iiber  Lahmungszustande  der  unteren  extremitaten 
und  deren  Behandlung.      Stuttgart,    1840. 
—  Spinale  Kinderlahmung.      2   Aufl. ,    Stuttgart,    i860. 

Hewitt.  On  acute  poliomyelitis  (Heine-Medin  disease).  Brit  Med.  Journ., 
Mar.  30,  1912. 

HlGIER.  Zur  klinik  der  Schweissanomalien  bei  Poliomyelitis  ant.  (Kinder- 
lahmung^ und  post.  (Herpes  Zoster).  Deutsch.  Zeitschr.  f.  Nerven- 
heilk., 2G,    1  go  1. 

HlLLlER,  S.  Epidemic  poliomyelitis  occurring  at  Stowmarket,  Suffolk. 
Brit.  Med.  Journ.,  Dec.  30,  1911. 

HLAVA.  Poliomyelitis  ant.  ac.  partialiter  hsemorrhagia.  Quoted  by  Jagic, 
Wien.  med.  Wochenschr.,  iSgg. 

HOCHE.      Uber     spinale     Kinderlahmung.       Arch.      f.      offentliche      Gesund- 

heitspflege  in  Elsass-Lothringen,  22,   1902,  S.  97. 
-—  Experimentelle    Beitrage    zur    Pathologie    des    Riickenmarks.     Arch.    f. 
Psychiatrie,  32. 

HOCHHAUS.     Uber  Poliomyelitis  acuta.     Munch,  med.  Wochenschr.,  46,  1909. 

HOFFMANN.  Cerebrale  und  spinale  Kinderlahmung  bei  Geschwistern. 
Munch,  med.  Wochenschr.,  50,  1904. 

-  Zur  Kenntniss  der  syphilitischen  akuten   und   chronischen   atrophischen 

Spinallahmung.      Neurol.    Zentralbl.,    igog. 

-  Tiber  eine  Epidemie  von  Poliomyelitis  ant.  ac.  in  der  Umgebung  Heidel- 

bergs   im   Sommer   und   Herbst,    igo8,   und   bemerkenswerte   Beobacht- 

ungen   aus  friiheren  Jahren.      Deutsch.   Zeitschr.    f.    Nervenheilk.,   30, 

Dec.  8,   igog. 
HOGYES,    Lyssa.     Spezielle    Pathologie    und    Therapie    von    Nothnagel.      5, 

AA'ien,   1897. 
HOHMANN.      Zur   Behandlung   des   Friihstadiums   der   Pol.    ant.    ac.     Munch. 

med.  Wochenschr.,  igog. 
Holt,    Emmet,    and    Bartlett.     The    epidemiology    of    acute    poliomyelitis, 

a   study   of   thirty-rive    epidemics.     Amer.    Journ.    of   Med.    Sc,    May, 

igoS. 
HOLT.      Some    clinical    features    of   epidemic   poliomyelitis.     Arch,    of    Ped., 

igio. 
HOMEN.      De   Paction   du   streptocoque   et    de    ses   toxines   sur  les   nerfs,    les 

ganglions    spinaux    et  la   moelle   epiniere.      Compt.    rend,    de    la    Soc. 

de  Biol.,  3,  1896,  10  ser.,  p.  518. 
HOMEN  and  LAITINEN.     Die  Wirkung  einiger  Bakterien  und  ihre  Toxine  auf 

periphere    Nerven,    Spinalganglion    und    das    Riickenmark.      Zieglers 

Beitr.,  25,   1899. 
HOUGH   and   LAFORA.      Some   findings   in   the    cerebrospinal   fluid   in   eleven 

cases  of  acute  anterior  poliomyelitis,  epidemic  form.     Fol.  Neurobiol., 

v,  191 1,  No.  3. 
Hounsfield.     Epidemic     uaralysis     (polioencephalo-myelitis).     Brit.      Med. 

Journ.,  Dec.   2,   1911. 
HOWELL.     A  case  of  acute  poliomyelitis  in  an  adult.      Lancet.  Sep.   15,   1911. 
HUET.      Un    cas   de    paralysie    spinale    infantile   avec    participation    du    nerf 

recurrent.     Rev.   neurol.,   igoo. 
HUISMANS.      Uber  die  Pol.  ant.  ac.      Deutsch.  Arztezg.,  Nov.   15,  1909. 

IBRAHIM  and  Herrmann.  Uber  Bauchmuskellahmung  bei  Pol.  ant.  ac.  im 
Kindesalter.      Deutsch.    Zeitschr    f.   Nervenheilk.,   4905. 

Immermann.  Uber  Pol.  ant.  ac.  und  Landrv's  Paralyse.  Neur.  Zentralbl.. 
1885. 

Jagic.  Zur  Kenntniss  der  akuten  Poliomyelitis  bei  Erwachsenen.  Wien- 
med.  Wochenschr.,  9  and  11,  i8gg. 


LITERATURE  1 87 

Jendrassic  and  Marie.     Contribution  a.  l'etude  de   l'hemiatrophie  cerebrale 

par  sclerose  lobaire.     Arch,   de  physiol.,  3. 
Job  and  Froment.     Rev.  de  Med.,  Paris,  igio,  30,  p.  162. 
JORG.      Uber     die    Verkriimmungen     des    menschlichen    Korpers    und     eine 

rationelle  Heilart  derselben.     Leipzig,  1810,  p.  85. 
JOEST    and    Degen.     Untersuchungen    uber    die    pathologische    Histologic, 

Pathogenese    und    post-mortale    Diagnose    der    seuchhaften    Gehirn- 

Riickenmarkserkrankung       (Bornaschen       Krankheit)       der       Pferde. 

Zeitschr.  f.  Hyg.  u.  Infect. -Krankh.  der  Haustiere,  9. 
JOGICHESS.    Zur  Epidemiologic  der  Pol.  ac.  ant.    Munch,  med.  Wochenschr., 

1910,  p.   2048. 
Johannessen.     Bemerkniger  om    Poliomyelitis    ant.    ac.     Norsk.    Mag.    for 

Laegevid.,  16,  p.  2gg,  1901. 
JOHNSON  and  Clarke.     On  a  remarkable  case  of  extreme  muscular  atrophy, 

&c.      Med.   Chir.   Trans.,  51,  London,   1868. 
JONES.     Infantile  paralysis  as  observed  in  health  district  No.  15  during  1909. 

Boston,    1910,   Wright  and   Porter  Printing  Co. 
JONNESCO.      Recherches     cytopathologiques     sur     les     ganglions     rachidiens 

dans  deux  cas  de  paralysie  spinale  infantile  de  date  ancienne.     Nouv. 

iconogr.  de  la  Salp.,  191 1,  No.  4. 

Kadyi.  Uber  die  Blutgefasse  des  menschlichen  Ruckenmarks.  Lemberg, 
1889. 

Kafka.  Zerebrospinalfhissigkeit  bei  Poliomyelitis.  Zeitschr.  f.  d.  gesamt. 
Neur.  xiii,  Heft  2. 

V.  Kahlden.  Uber  Entzundung  und  Atropine  der  Vorderhorner  des  Rucken- 
marks.     Zieglers  Beitr.,   13,  p.   113,   1893. 

—  Neuere  Arbeiten  iiber  Poliomyelitis  anterior  acuta.      Zentralbl.   f.   allg. 

Path,  und  path.  Anatomie,  5,  1894. 
-  Uber    Entzundung   und    Atropine    der    Vorderhorner    des   Ruckenmarks. 

Verhandl.  d.  Kongress  f.  inn.  Med.,  1901. 
Kaiserliches  Gesundheitsamt.      Ratschlage  an  Arzte  fiir  die  Bekampfung 

der    akuten    epidemischen    Kinderlahmung     (Poliomyelitis    acuta    in- 
fantum).     Berlin,    1910. 
Kalischer.     Uber  Teleangiektasien  mit  unilateraler  Hypertrophic  und  liber 

Knochenverlangerung    bei    spinaler    Kinderlahmung.     Monatsschr.    f. 

Psych,  u.   Neurol.,   1899. 
KANDUTSCH.      Einige  Erfahrungen  iiber  Heine-Medinsche  Erkrankungen  im 

Bezirk    Deutsch-Landsberg     (Steiermark).     Der    Amtsarzt.,    ii,     19 10, 

No.   11. 
Kawka.      Beitrag  zur  pathologischen  Anatomie  der  spinalen  Kinderlahmung. 

Inaug-Diss.,   Halle,    1889. 
Kennedy.     Recherches  sur  quelques  formes  de  paralysie,  qui  se  manifestent 

chez  les  enfants.     Arch,  gener.  de  Med.,  4  serie,  23,  p.  311,  1850. 

—  On   some  of  the  forms  of  paralysis   which  occur  in   early  life.     Dublin 

Quarterly  Journal,  g,  1850,  and  22,  1861. 
Kerr.     The  infectiousness   and    contagiosity   of    acute    poliomyelitis.     New 

York  State  Journ.  Med.,  igog. 
KEY   and   RETZIUS.      Studien   in    der   Anatomie    des   Nervensystems   und    des 

Bindegewebes.     Stockholm,   1875-76. 
Kling,    Wernstedt,   and   Pettersson.     Recherches   sur   la  mode   de  propa- 
gation de  la  paralysie  infantile  epidemique  (maladie  de  Heine-Medin). 

Zeitschr.  f.   Immunitatsforschung  u.  Experiment.      Therapie  xii,  igi2. 
Knoepfelmacher.     Experimentelle  Ubertragung  der  Pol.  ant.  ac.  auf  Affen. 

Med.  Klinik,  44,  1909. 
KOPLIK.     Akute   Poliomyelitis   (an  epidemy).     Arch,  of   Ped.,  May,    1909. 
Kramer.     Die  spinale  Kinderlahmung.     Med.   Klin.,  52,   igog. 
Kraus.     Uber  das  Virus  der  Poliomyelitis  acuta,  zugleich  ein   Beitrag  zur 

Frage  der  Schutzimpfung.      "YVien.  klin.   Wochenschr.,  7,   1910. 

—  Uber  filtrierbares  Virus  iiber  das  Wesen  der  Poliomyelitis  acuta.     Med. 

Klin.,  12,  igio. 

—  Experimentelle  Beitrage  zur  Frage  der  Schutzimpfung  bei  Poliomyelitis 

acuta.      Zeitschr.   f.   Immunitatsforschung,  9,  2. 
Krause,  P.     Zur  Kenntniss  der  westfalischen  Epidemie  von  akuter  Kinder- 
lahmung.    Deutsche  med.    Wochenschr.,  42,    igog. 

—  Kurze  Mitteilung  iiber  die  rheinisch-westfalische  Epidemie  von  akuter 

Kinderlahmung.      Verhandl.    d.   Kongress   f.    inn.    Med.,    Wiesbaden, 
igio. 


1 88  EPIDEMIC    INFANTILE    PARALYSIS 

KRAUSE,    P.      Die    akute    epidemische    Kinderlahmung-Therap.    d.    Gengen- 
wart.,  iqii,  Nos.  4  and  5. 

KRAUSE    and    MEINICKE.      Zur    Atiologie   der    akuten    epidemischen    Kinder- 
lahmung.    Deutsche  med.  Wochenschr.,  42,   iqoq 

Zur   Atiologie    der    akuten    epidemischen    Kinderlahmung.      II.    Mit- 

teilung.     Deutsche  med.  Wochenschr.,   14,   iqio. 

Laborde.     De  la  paralvsie   (dite  essentielle)  de  l'enfance.     These  de  Paris, 

1864. 
LAMY.      Sur   un    cas    d'encephalite    corticale    et    de    poliomyelite    anterieure 

associees.     Rev.  neurol.,  1894. 

—  Sur   les   lesions  medullaires  experimentales  produites   par   les   embolies 

aseptiques.     Arch,    de  physiologie  normale  et  pathologique,    1895   and 

1897.  .. 
LANDOLT.      Uber   einen    aussergewohnlichen    Fall   von    Pol.   ac.    ant.    Korre- 

spondenzbl.  f.   Schweitz.  Arzte.      No.  33. 
Landsteiner.     K.k.   Gesellschaft  der  Wiener  Arzte,   Dec.    18,    1908. 

—  Bemerkungen  zu  der  Mitteilung  von  P.   Krause  und   E.   Meinicke ;   Zur 

Atiologie  der   akuten   epidemischen    Kinderlahmung.      Deutsche   med. 
Wochenschr.,   1909,  p.    1975, 
-  Technik    der    Untersuchungen     liber     Poliomyelitis     acuta.      I    Erganz- 
ungsband  des  Handbuches  der  Technik  und  Methodik  der  Immunitats- 
forschung.    Jena,  191 1.     G.   Fischer. 

—  Diskussionsbemerkungen    auf     der     4     Tagung     der     Vereinigung     fur 

Mikrobiologie.     Zentralbl.  f.  Bakt.,  47.  Ref. 
Landsteiner  and  Levaditi.     La  transmission  de  la  paralysie  infantile  aux 
singes.      Compt.   rend.   Soc.  biol.  a  Paris,   Nov.   27,   1909. 

-  La  paralysie  infantile  experimentale.     Ibid.,  Dec.   18,  1909. 

La  paralysie  infantile  experimentale.      Ibid.,  Jan.  3,  1910. 

La  paralysie  infantile  experimentale.     Ibid.,  Jan.  10,  1910. 

-  La  paralysie  infantile  experimentale.      Ibid.,  Feb.   iq,  1910. 
—  La  paralysie  infantile  experimentale.      Ibid.,  March  5,   1910. 

Etude   experimentale   de   la    Poliomyelite  aigue    (Maladie  de   Heine- 

Medin).     Ann.  Pasteur,  1910,   11. 
Landsteiner,  Levaditi,  and  Pastia.     Recherches  du  virus  dans  les  organs 

d'un  enfant  atteint   de  poliomyelite   aigue.     Acad,    des   sciences,   June 

12,    1911. 
Landsteiner    and    Popper.     Ubertragung    der    Pol.     ant.     ac.     auf    Affen. 

Zeitschr.   f.    Immunitatsforschung,  2. 
Landsteiner  and  Prasek.     Ubertragung  der  Poliomyelitis  acuta  auf  Affen. 

II.  Mitteilung.      Zeitschr.  fur  Immunitatsforschung,  4,  1910. 
LANGE.      Zur    Behandlung    des    Friihstadiums    der    Poliomyelitis.       Munch. 

med.  Wochenschr.,  49,   1909. 
LANGER.      Schule  and  Kinderlahmung.     Jahrb.   f.  Kinderheilk.,  lxxvi,  2. 
LANGERMANN.      fiber  das  Vorkommen  von  epidemischer  Kinderlahmung  im 

Kreise    Giessen.     Korrespondenzbl.    d.    arztl.    Vereine    des    Grossher- 

zogtums  Hessen,   12,   1909. 
Langhorst.     Poliomyelitis.     Journ.  of  Amer.  Med.  Assoc,  Dec.  28,  1912. 
LASCH.      Zur   Epidemiologic   der   Poliomyelitis   ant.    ac.      Der  Amtsarzt,    11, 

LEAVITT.      Report   of    some    rather    infrequent    cases    occurring    in    obstetric 

practice.     North  Western  Lancet,  Sept.,  1,  1902. 
LEBREDO  Y   RECIO.      Poliomyelitis   anterior   aguda   epidemica.      Epidemia   de 

Cuba,  1909.      Sanidad  y  beneficiencia,   1910. 
Leegaard.    Om  poliomyelit  med.  demonstration  af  mikroskopiska  praparater. 

Forhandl.  paadet  3  norske  lsegemode  i  Bergen,  August,   1889,  p.  73. 

—  Beretning  om  en  epidemi  of   Poliomyelitis   anterior   acuta   i   Bratsberg 

amt  aar,  1899.      Norsk.  Mag.  for  Laegevid.,   16,  iyoi,  p.  377. 

—  Etgammelt    aktstykke    Pol.     in    Norway    at    1868.       Norsk.     Mag.     for 

Laegevid.,  Nov.  1907. 

—  Kliniske  og  epidemiologiske  underscegelser  over  den  akute  poliomyelit 

i  Norge  Videnskebs  Aelskabets.      Strifter  Christiania,   igog. 
Leiner     and    v.     Wiesner.     Diskussionsbemerkungen     zum     Vortrage     des 
Herrn    Zapport  :    Poliomyelitiserkrankungen    in    Wien.      Gesellsch.    f. 
inn.    Med.    und   Kinderheilk.    zu.    Wien.      (Padiatr.    Sekt.),    Nov.     18. 
igog.     Berl.  klin.  Wochenschr.,  51,  igog. 


LITERATURE  1 89 

Leiner  and  v.  Wiesner.  Experimentelle  Untersuchungen  iiber  Poliomyelitis 
acuta.     Wien.  med.  Wochenschr,  42,  1910. 

Experimentelle    Untersuchungen    iiber    Poliomyelitis    acuta    inferior. 

Wien.  klin.  Wochenschr.,  ag,  igog;  3,  g  and  22,  igio. 
Lentz     and     Huntemuller.       Uber     akute     epidemiscbe     Kinderlahmung. 
Zentralbl.   f.   Bakt.,  47,    1910,   Ref. 

Experimentelle  Poliomyelitis.     Zeitschr.  f.  Hyg.  u.   Infekt.-Krankh., 

56,  3,  1910. 

—  Diskussionsbemerkungen  bei  der  Tagung  d.   Freien  Vereinigung  fur 
Mikrobiologie.     Zentrabl.  f.   Bakt.,  47,  Ref. 

Leri  and  Wilson.  Un  cas  de  poliomyelite  anterieure  aigue  de  Fadulte  avec 
lesions  medullaires  en  foyers.     Nouv.   iconogr.   de  la  Salp,  1904. 

LEVADITI  and  LANDSTEINER.  Recherches  sur  la  paralysie  infantile  experi- 
mentale.     Comptes  rend.   Soc.   de  Biol.,  a  Paris,  Jan.  3,   1910. 

—  Etude  experimentale  de  la  poliomyelite  aigue.      Ibid.,   lxviii,  p.   417. 
Action  exercee  par  le  thymol,  le  permanganate  de  potasse  et  l'eau 

oxygenee  sur  le  virus  de  la  poliomyelite  aigue.     Ibid.,  April  30,  1910. 
Levaditi  and  Stanesco.     Paralysie  faciale  provoquee  chez  le  singe  par  le 
virus  de  la  poliomyelite  aigue.     Comptes  rend.  Soc.  de  Biol.,  a  Paris, 
Feb.   12,   iqio. 

—  Lesions  nerveuses  et  atrophie  musculaire  chez   les  singes   atteintes   de 

paralysie  infantile.      Ibid.,  April   16,    1910. 
Levaditi.     Essais  de  culture  du  rjarasite  de  la  paralysie  infantile.     Presse 
med.,  1910,  6. 

—  L'etude  experimentale    de    la    poliomyelite    aigue.     Presse    med.,    1910, 

33  and  41. 

—  The    recent    epidemiological   and  experimental    researches    on    infantile 

paralysis,     journ.   of  the  Royal  Institute  of  Public  Health    19,    191 1, 

i-3- 
LEWANDOWSKI.     Die  Heine-Medinsche  Krankheit,  bsw.  akute  Poliomyelitis. 

Jahrb.  f.  Kinderheilk. ,  73,  Heft  4. 
Leyden.     Beitrage  zur  nathologischen  Anatomie  der  atrophischen  Lahmung 

der  Kinder  und  Erwachsenen.     Arch.   f.  Psychiatrie,   1876. 

-  Uber  Poliomyelitis  und  Neuritis.     Ill  Kongress  f.  inn.  Med.  Berl.  klin. 

Wochenschr.,  20,   1884. 
v.   Leyden  and  Goldscheider.      Spez.   Pathologie  und  Therapie  von  Noth- 

nagel,  10,  2. 
V.     Leyden    and    Redlich.       Myelitis    acuta.     Referate.     Kongress    f.     inn. 

Med.,  Berlin,   1901. 
Lhermitte.      De   la   multiplicite    des   lesions   et    des    symptomes    de   la    soi- 

disant     poliomyelite    anterieure     aigue     epidemique.      Semaine     med., 

47,   1909. 
LlXDER  and  Mally.     Zur  Poliomyelitisepidemie  in  Ober-Osterreich.  Deutsche 

Zeitschr.  f.  Nervenheilk.,  38,  1910. 
Locker.     Die  Poliomyelitisepidemie  im  osterreichischen  Landbezirke  Steyr. 

Das  osterreichische  Sanitatswesen  Jahrg.  21,  1909.     Beilage  zu  No.  49, 

P-  7I- 
LOVEGREN.      Bidrag   till    Kannedcmen    om    Poliomyelitis    ant.    ac.    och   nara 

staende    sjukdomsformer.      Compt.    rend.    Congres   Helsingfors,    1908, 

p.   48. 

—  Zur  Kenntniss  der  Pol.  ant.  ac.  und  subac.   s.   chron.     Jahrb.  f.  Kinder- 

heilk. u.  psych.   Erzieh,  61,   1905,  H  2. 
LOOFT    and    Dethloff.       To    tilfalde    af    poliomyelitis    ant.    ac.    hos    born. 

Lumbalpunktion.      Bakteriologisk.      Untersogelse      at      spinalvadsken. 

Medicinisk  Rev.,  igoi. 
LOVETT.     A  study  of  anterior  poliomyelitis  with  analysis  of  647  cases  from 

the  Children's  Hospital,  Boston.     Med.   Record,  73,  p.    1098. 

—  Occurrence    of    Infantile    Paralysis    in    Massachusetts  in    1907.     Boston 

Med.  and  Surg.  Journ.,  July  20,  1908. 

-  Infantile  Paralysis.     Journ.  of  Amer.   Med.  Assoc,   1908,  No.   20. 

—  The  occurrence  of  Ant.    Pol.   in  Massachusetts  in    1907.     Med.    Record, 

74,   I9o8j  P-  779- 

—  The  occurrence  of  infantile  paralysis  in  Massachusetts.     Boston,    1910. 

Wright  and  Porter  Printing  Co. 

LOVETT  and  EMERSON.  The  occurrence  of  infantile  paralysis  in  Massa- 
chusetts in  1908.      Boston  Med.  and  Surg.  Journ.,  July  12,  igog. 

LOVETT  and  Lucas.  A  study  of  635  cases  of  infantile  paralysis.  Journ.  of 
Amer.  Med.  Assoc,  igo8. 


190  EPIDEMIC    INFANTILE    PARALYSIS 

LOW,  H.  B.     Acute  Poliomyelitis.     An  analysis  of  sixty-two  cases  occurring 

in  and  around  Edinburgh  in  the  epidemic  of   1910.      Proc.    Roy.    Soc. 

Med.,  Feb.,  1912.      Clin.  Sec,  p.  76. 
LUCAS.     The    diagnosis   of   infantile  paralysis  in   the   prodromal   and   early 

acute  state,  &c.     Journ.  Amer.  Med.  Assoc,  1908. 
LUNDGREEN.      Om    den    s.    k.    akuta    barnfornlamningen    i    Vaxjo   provinsial 

lakare-distrikt  ar  1905.     Hygiea  N.F.   II.   Jg.   6,   1906,  p.    1089. 

MACHOL.      Die  chirurgisch-orthopadische   Behandlung   der   spinalen   Kinder- 
lahmung.     Munch,    med.    Wochenschr.,    1910. 
McCLANAHAM.     A   brief    report   of   the    Nebraska  epidemic   of   poliomyelitis. 

Journ.  of  Amer.  Med.  Assoc,  55,  1910,   14. 
MACKENZIE.      Epidemic    Poliomyelitis,    with    a    report    of    ten    cases.     Med. 

Record,  62,  1902,  p.   528. 
Macphail.     A    preliminary    note    on   an    epidemic    of    paralysis    in   children 

Brit.   Med.  Journ.,  Dec,   1894. 
Marburg.     Zur  Pathologie  der  Poliomyelitis  acuta.     Wien.  klin.  Rundschau, 

47,  1909. 
Marchand.      Uber  einen   Fall  von   akuter   Poliomyelitis  bei   einem   Erwach- 

senen.     Munch,   med.    Wochenschr.,    1910. 
Marie,    Pierre.     Hemiplegie  cerebrale    infantile    et    maladies    infectieuses. 

Progres  med.,   1885. 
— ■  Legons  sur  les  maladies  de  la  moelle.     Paris,    1892. 
— ■  La     paraplegie     cerebrale    infantile.      Bull,     et     mem.     Soc.     med.     des 

hopit.,   1902. 

—  Sur   la   coincidence,    chez  un   meme   malade   de   la   paraplegie  cerebrale 

infantile  et  de  la  paralyse  spinale  infantile.     Idem.,  1902. 
Marie,    Pierre  and  Marinesco.     Sur  un  cas  de  paralysie  de  Landry  avec 

constation   dans  les  centres  nerveux   de   lesions  poliomyelitiques  liees 

a  la  presence  d'un  microbe.      Semaine  med.,    1895. 
MARINESCO.      Contribution  a  Tetude  de  la  nevrite  ascendante.      Presse  med., 

1898. 

—  Beitrag    zur    Lehre    von    der    infantilen    Hemiplegie.       Deutsche    med. 

Wochenschr.,  16,  1902. 

-  De  la  transmission  du  virus  de  la  poliomyelite  par  le  nerf  peripherique 

et   ses   rapports   avec   les   infections  ascendantes.     Compt.    rend.    Soc. 
de  Biol.,  a  Paris,  Feb.  25,  1911. 

—  Sur  l'histologie  fine   de  la  poliomyelite   experimentale.      Ibid.,   Dec    15, 

19 10. 

—  Transmission   du   virus   de   la   poliomyelite  par   le   sympathique.      Ibid., 

May  27,  191 1. 
Marks.      Infection    of    rabbits    with    the   virus    of    poliomyelitis.     Journ.    of 

Experiment.  Med.,  14.  1911,  No.  2. 
MARTIUS.     Uber  spinale  Kinderlahmung.     Arztl.  Verein  Rostock  ref.  Munch. 

med.  Woch.,  iqio,  15. 
MATTHES.      Sektionsbefund     bei     einer     frischen     spinalen     Kinderlahmung. 

Zeitschr.  f.  Nervenheilk.,   13,   1898. 
MAYER.      Die  Behandlung  der  frischen  Kinderlahmung  durch  Ruhigstellung. 

Deutsche  med.  Wochenschr.,  24,  1911. 

—  Epidemic  poliomyelitis.     Med.  Record,  79,   1911,  No.  7. 

MEDIN.      Uber  eine   fipidemie    von    spinaler    Kinderlahmung.      X.    Internat. 
med.  Kongr.      Berlin,  1890. 

-  Om  den  infantile  paralysien.      Nord.  med.  Ark.,  28,   1896,   1. 

-  L'etat   aigu  de   la   paralysie  infantile.     Arch,    de   med.    des   enf.      May- 

June,    1898. 
MEINICKE.      Zur      Atiologie      der      akuten      epidemischen      Kinderlahmung. 
Rheinisch-westfalische   Gesellschaft   ftir  innere  Medizin   und  Nerven- 
heilk., Nov.    14,   1909.      Munch,  med.  Wochenschr.,   1,   igio. 

-  Experimentelle      Untersuchungen      uber     akute      epidemische     Kinder- 

lahmung.      Deutsche  med.  Wochenschr.,  15,  1910. 

-  Praktische  Ergebnisse  der  experimentellen  Untersuchungen  iiber  akute 

epidemische  Kinderlahmung.     Kongr.  f.   inn.  Med.,  Wiesbaden,   1910. 
MEYER,  M.     Die  elektrizitat  in  ihrer  Anwendung  auf  die  praktische  Medizin. 
Second  edition.      Berlin,   1861,  p.   207. 

—  Uber  die   Heine-Medinsche   Krankheit    (spinale   Kinderlahmung)   in   der 

Provinz   Schleswig-Holstein  in  den  Jahren   igog-10.     Arch.   f.    Kinder- 
heilk.,  56,  3. 


LITERATURE  191 

MlDDLETOX.      Glasgow  Med.  Journ.,  June,   1804. 

MlLHIT.      La  paralysie  soinale  infantile.      Progres  med.,   191 1,   >,o.    13. 

MITCHELL.     Poliomyelitis    in    the     adult.      Involving    all    four    extremities. 

Journ.  of  Nerv.  and  Ment.  Dis.,  1903,  p.  48g. 
MODEXA.      Polyneuritis  and  Poliomyelitis.     Monatsschr.  f.  Psych,  u.  Neurol., 

2g,  Heft  2. 
MOBIUS.      Schmidt's   Jahrbucher,   1884. 
Moxckeberg.     Anatomische  Befund  eines  Falles  von  "  Landryschem  Sym- 

ptomenkomplex.';'     Munch,   med.   Wochenschr.,  45,   1903. 
MOIR,    J.    H.     Epidemic   anterior   poliomyelitis  in    South   Derbyshire.      Brit. 

Med.  Journ.,  Dec.  30,  191 1. 
MONEY.      The   spinal   cord   of   a   recent  and   an   old   case   of  infantile   palsy. 

Trans.   Path.   Soc.  of  London,  35,   1884. 
Morse.     Acute  poliomyeloencephalitis.     Med.   and  Surg.   Journ.,    164,    1911. 

—  Der    Wert    der    Lumbalpunktion    und    der    Leukocytenzahlung    bei    der 

Poliomyeloencephalitis.     Arch,  of  Ped.,   28,   191 1. 
MOTT.     Microscopical    examination    of    the    spinal    cord,    peripheral    nerves 

and  muscles  in  a  case  of  acute  poliomyelitis.     Arch,  of  Neurol.,  1S99. 
MULLER,  A.      Eine  epidemische  auftretende  Erkrankung  des  Nervensystems 

auf  Nauru.     Arch.   f.    Schiffs.   u.   Tropenhyg.,    1910. 
MULLER,  ED.      Uber  die  Friihstadien  der  spinalen  Kinderlahmung.      Miinch. 

med.  Wochenschr.,  48,  1909. 
— ■  Die  spinale  Kinderlahmung.      Berlin,   1910,  Julius  Springer. 

—  Uber  die  epidemische  Poliomyelitis.     Arch.  f.  Kinderheilk.,  53. 

—  Die    serodiagnose    der    epidemischen    Kinderlahmung.     Deutsche    med. 

Wochenschr.,  24,   ign. 

—  Fruhstadium     der     Kinderlahmung.     Monatsschr.     f.     Kinderheilk.,     xi, 

No.  7. 

—  Epidemiologic    der    spinalen    Kinderlahmung:       Deutsche    Zeitschr.     f. 

Nervenheilk.,  45,  Heft  3. 

—  Bulbare  Form  der  epidem.  Kinderlahmung.     Miinch.  med.  Wochenschr., 

4,  1912. 
Muller,  Franz.     Die  akute  atrophische  spinale  Lahmung  der  Erwachsenen 
(Poliomyelitis  acuta  anterior).      Wien,   i8go. 


NANXESTAD.      Epidemie    von    Poliomyelitis   ant.    ac.    im    Bezirk    Hvaler    im 
Sommer  1904.      Norsk.  Mag.  for  Laegevid.,  No.  4. 

—  Beretning  om  en  epidemi  of  Pol.   ant.    ac.   i  Hvaler  laegedistrikt  som- 

meren  1904.      Norsk.  Mag.  for  Laegevid.,  3  R.  4,  1906    p.  409-424. 
Negri,  quoted  by  Wickman. 
NETTER.      Frequence   insolite   des   Poliomyelites  en    France   pendant   l'ete   et 

l'automne  igog.     Bull,  et  mem.  Soc.  med.  des  hopit.,  Nov.   12,   ig,  26, 

igog. 

—  Unicite  vraisemblable  de  la  poliomyelite  epidemique  et  de  la  paralysie 

infantile  spinale.      Ibid.,  10,  Dec.  31,  igog. 

—  Apparation  sous  forme  epidemique   de  la  paralysie  infantile   a.  Paris  et 

sa  banlieue  en  igog.     Bull,  de  FAcad.   de  med.,  May  31,   1910. 

—  Meningites  benign.es  d'allure  epidemique.      Bull,   et  mem.   Soc.  med.   des 

hopit.,  Oct.  21,  igio. 

—  Paralysies  infantiles  a  debut  meningitiques.      Formes  meningitiques  de 

la  maladie  de  Heine-Medin.      Ibid.,   Nov.    iS,   1910. 
Netter,    Gendron,    and    Fouraine.      Serotherapie   de   la   poliomyelite   ante- 

rieure    aigue.      Compt.    rendu    des    seances    de    la    Soc.    de    Biol.,    70, 

pp.  625,  707,  739. 
Netter  and  Levaditi.     Action  microbicide  exercee  par  le  serum  des  malades 

atteints  de  paralysie  infantile  sur  le  virus   de  la  poliomyelite  aigue. 

Compt.  rend.  Soc.  biol.  a  Paris.  xApril  g,   igog. 

—  Action  microbicide  exercee  sur  le  virus  de  la  poliomyelite  aigue  par  les 

serums    des    sujets     anterieurement    atteints     de     paralysie    infantile. 
Ibid.,  Mav  21,  igio.  , 
Netter   and  Tinel.     Des   modes   de   debut  de   la   poliomyelite   aigue   et   en 
particulier    de    ses    formes    meningitiques.      Association    francaise    de 
pediatrie.      Congres  de  igio. 

—  Poliomyelite  anterieure  aigue   de   l'adulte.      Poliomyelite  chez  la  femme 

enceinte.      Bull,  et  mem.  Soc.  med.  des  hopit.,  Mar.  24,  ign. 


I92  EPIDEMIC     INFANTILE     PARALYSIS 

NEURATH.  Ein  Fall  von  infantiler  Hemiplegie  mit  poliomyelitischer  Lah- 
mung  des  zweiten  Beines.      Wien.   med.   Presse,  igoo. 

-  Demonstration  eines  Falles  von  Pol.  acut.     AVien.   med.   Klub.,   Xov.   8, 

1899,  Wiener  med.  Presse. 

-  Uber    seltenere    Knochendeformitaten    nach     spinaler     Kinderlahmung. 

AVien.  med.  Presse,  igoi. 
Xeurath.     Beitrage  zur  Anatomie  der  Pol.  ant.  ac.  Arb.  a.  d.  Neurol.    Instit. 
a.  d.  AViener  Univers.,  12,  p.  297,  1905. 

—  Klinische  Studien  iiber  Pol.   II.  Klinische  VJntersuchung  an  240  Fallen 

von  spinalen  Kinderlahmung.    Jahrb.  f.  Kinderheilk.,  61,  Heft  5,  1905, 
p.  742. 

—  Atypische  Poliomyelitisfalle.     AA^ien.   klin.   AA'ochenschr. ,   1909. 

—  Erfahrungen    wahrend     der    Poliomyelitisepidemie     1908-09    in    Wien. 

Wien  klin.  AVochenschr.,  22  and  37,  1909. 
Xeustadter.     Acute  Poliomyelitis.     Journ.   of  Amer.   Med.   Assoc,   Sept.  7, 

1912. 
Xeustadter  and   Thro.     Experimental  poliomyelitis  produced  in  monkeys 

from  the  dust  of  the  sick-room.     Proc.  of  the  New  York  Path.  Soc,  9, 

191 1,  Nos.  3  and  4. 
Xew  York  Report  on  the  epidemic  of  1907. 

Xewmark.     A  little  epidemic  of  poliomyelitis.     The  Med.  News,  1899. 
Xiedxer.     Ein    Fall    von    Poliomyelitis    acuta    der    Erwachsenen.     Munch. 

med.  AArochenschr.,  18,  1898. 
NIEMANN.      Poliomyelitis  acuta.      Charite  ann.,  xxxvi. 
XOBECOURT  and  Darre.      Reactions  meningees  anatomiques  et  cliniques  a  la 

suite  de  l'injection  intraxachidienne  du  serum  humain  dans  un  cas  de 

maladie  de  Heine-Medin.     Compt.  rend.  Soc.  biol.  a  Paris,  69. 
XONNE.      Riickensmarkerkrankungen  in  Fallen  von  pernicioser  Anamie,  von 

Sepsis  und  von  Senium,  usw.     Deutsche  Zeitschr.  f.   Xervenheilk.,  14, 

1899. 

Oettinger  and  Marinesco.  De  l'origine  infectueuse  de  la  paralysie 
ascendente  aigue  ou  maladie  de  Landry.     Semaine  med.,  1895^ 

Oppenheim.  Uber  die  Poliomyelitis  anterior  chronica.  Arch.  f.  Psvchiatrie, 
19,  1888,  p.  381. 

—  Zur  Pathologie  der  chronischen  atrophischen  Spinallahmung.     Arch.    f. 

Psychiatrie,  24,   1892. 

—  Zur    Encephalitis    pontis    des    Kindesalters,    zugleich    ein    Beitrag    zur 

Symptomatologie     der     Facialis-     und     Hypoglossus-lahmung.     Berl. 
klin.    AVochenschr.,    1899. 
— ■  Lehrbuch  der  Nervenkrankheiten,   1908. 

OSGOOD  and  LUCAS.  Transmission  experiments  with  the  virus  of  polio- 
myelitis.    Journ.  of  Amer.  Med.  Assoc,  56,   1911,  No.   7. 

Oulment  and  BAUDOUIN.  Poliomyelite  anterieure  a.  rechute.  Role  possible 
d'un  traumatisme  anterieur.     Rev.   neurologique,    191 1,   No.   6. 

Oxholm.  Tilfaelde  af  omtrent  samtidig  optraedente  Lammelse  hos  Born. 
Tidskrift.  f.  prakt.  Med.,  1887. 

Packard.  Acute  anterior  poliomyelitis  occurring  simultaneously  in  a 
brother  and  sister.     Journ.  of  Nerv.  and  Mental  Dis.,   1899. 

Painter.  An  epidemic  of  infantile  paralysis.  Boston  Med.  Journ.,  Dec.  11, 
1902. 

Parker.  An  epidemic  of  infantile  paralysis  in  Bristol.  Brit.  Med.  Journ., 
Mar.   iS,  1911. 

Parrot  and  Joffroy.  Note  sur  un  cas  de  paralysie  infantile.  Arch,  de 
physiol.   norm,   et  path.,  3,   1870,  p.   309. 

PASTEUR.  An  epidemic  of  infantile  paralysis  occurring  in  children  of  the 
same  family.      Trans,   of  Clin.   Soc,  30,  London,   1897. 

Pasteur,  Foulerton,  and  MACCORMAC.  Etiology  of  acute  poliomyelitis. 
Lancet,   1908. 

Paul.  The  treatment  of  acute  poliomyelitis.  Med.  and  Surg.  Journ.,  164, 
191 1. 

Peabody,  Draper,  and  Dochez.  Acute  Poliomyelitis.  Monogr.  Rocke- 
feller Inst.,  No.  4. 

Peiper.  Das  Auftreten  der  spinalen  Kinderlahmung  (Heine-Medinsche 
Krankheit)  in  Vorpommern.      Deutsche  med.  AArochenschr. ,  g,   igio. 


LITERATURE  193 

Perkins   and   Dudgeon.     A   case   of   acute   poliomyelitis  in    an   adult   with 

marked  bulbar  and  ocular  symptoms.     Microscopical  report.     Brain, 

117,    1907. 
Petit   fils.     Considerations    sur    Fatrophique    aigue    des    cellules    motrices. 

Paris,   1873. 
PETREN.        Till    fragen    om   poliomyelitis   kliniska    srallning,    dess    prognos 

och  therapi.      Nord.   Tidskr.   f.   Therapi,   1909. 
Petren  and  Ehrenberg.     Etudes  cliniques  sur  la  poliomyelite  aigue.     Nouv. 

iconogr.  de  la  Salp.,  1909. 
PETTERSEN.     Epidemisk.    poliomyelit    i    Lier,    iqo6.      Tidskrift    f.    d.    norske 

laegeforening,   1908,  pp.  393,  444. 
PlERRACINI.       Una    epidemia    di    paralisi    atrophica    spinale    infantile.       Lo 

Speriment,   1895. 
PlOTROWSKA.      Contribution   a  l'etude  anatomique   de   la  paralysie  infantile. 

These  de  Paris,   191 1. 
PlRlE,  J.  Harvey.     A  case  of  rapidly  fatal  acute  poliomyelitis  in  an  adult. 

Rev.  of  Neurol,  and  Psychiat.,  Edinburgh,  1910. 
PLACZEK.      Beitrag    zur    spinalen    Kinderlahmung.      Berl.    med.     Gesellsch., 

May  8,   1901  ;  Deutsche  med.  Wochenschr.,  21,   1901. 

—  Zur  pathologischen  Anatomie  der  spinalen  Kinderlahmung.      Berl.  klin. 

Wochenschr.,  44,  igoi. 
PLATOU.      Nogle   oplysninger   om    en    epidemi   af   pol.    ant.    ac.   i    Aafjorden 

hosten,  1904.      Tidskrift  f.  d.  norske  laegeforening,  1905. 
PleuSS.      liber     gehauttes    Vorkommen    spinaler    Kinderlahmung.      Diss., 

Kiel,  1899. 
POTPESCHXIGG.      Bakteriologische  Untersuchungsergebnisse  bei  Poliomyelitis 

(Heine-Medinsche  KrankheitJ.      Wien.   klin.   Wochenschr.,  30,   1909- 

—  Beobachtungen   und  Untersuchungsergebnisse   aus   der   steiermarkischen 

Poliomyelitisepidemie    im    Jahre     1909.       Arch.     f.     Kinderheilk.,     54, 

1910. 
Praetoritjs.     Zur  pathologischen  anatomie  der  Poliomyelitis  ant.  ac.  infant. 

Jahrb.  f.  Kinderheilk.,  58,  1903;  supplement  to  Heft  1. 
Prevost  and  Vulpian.     Observation   de  paralysie   infantile.     Compt.   rend. 

de  la  Soc.  de  Biol.,  Dec,  1865. 
PROBST,     Uber    die    Folgen    der    soinalen    Kinderlahmung    auf    die    hoher 

gelegenen  Nervenzentren.     Wien.  klin.  Wochenschr.,  1898. 
Proscher.     Zit  nach  Fox. 
Purckhammer.     Zur     Frage     der    poliomyelitischen     Lahmungen.     Miinch. 

med.  Wochenschr.,  22,  191 1. 
PUSCHNIG.     Die  poliomyelitisepidemie  des  Jahres  1909-10  in  Karnten.     Das 

oesterreich.   Sanitatswesen,   191 1,   12  and  16. 

RANCKEX.  Nagra  fall  af  "  barnforiamning  "  behandlade  med.  "  banande 
ofningsterapi."     Finska   Lakarasellsk.   Handl.,    1909. 

RAUZIER.  La  reviviscence  des  poliomyelitis.  Journ.  de  med.  int.,  191 1, 
No.  12. 

Raymond.  Paralysie  infantile.  Atrophie  musculaire.  Compt.  rend,  de  la 
Soc.  de  Biol.,  1S75. 

—  La  paralysie   ascendante   aigue   dans   ses   rapports   avec  la   poliomyelite 

anterieure    et    la    Dolynevrite    motrice.     Lecons    sur    les    maladies    du 

systeme  nerveux.     Paris,  1897. 
Raymond   and  Sicard.     Meningite   cerebrale    spinale   a  forme   de    paralysie 

infantile,   cytodiagnostic.      Rev.   neurol.,    1902. 
Reckzeh.     Die    akute    spinale    Kinderlahmung    im    rheinisch-westfalischen 

Industrie-bezirk.     Med.   Klin.,  45,   1909. 
REDLICH.      Beitrag  zur    pathologischen    Anatomie   der    Pol.    ant.    ac.    infant. 

Wien.  klin.  Wochenschr.,  1894. 
REECE.      Certain  aetiological  considerations  arising  from  observations  of  the 

behaviour  of  poliomyelitis  in  Devon  and  Cornwall,    1911.      Proc.  Roy. 

Soc.    Med.    (Epidem.    Sec),    Feb.,    1912.      Report  to   L.G.B.    on   Public 

Health,  New  Series,  No.  61,  1912. 
Renault.     Une   epidemie  de  poliomyelite   dans   la   Creuse.     Soc.    med.    des 

hopit.,  Mar.  24,   1911. 
Renault  and  Martingay.     Poliomyelite    aigue    chez    une    femme    enceinte. 

Soc    med.  des  hopit.,  Mar.  24,  iqii. 
V.    REUSS.      Ein    Fall   von    Paralvsis    ascendens    Landrv.     Char.    Ann.,    23, 

1898. 

13 


194  EPIDEMIC    INFANTILE    PARALYSIS 

Rilliet  and  Barthez.       Traite  des  maladies  des  enfants.       2,   Paris,   1843, 

P-  335- 
— ■  —  Traite  des  maladies  des  enfants.      Second  edition,  Paris,   1861. 
Rissler.     Zur  Kenntniss  der  Veranderungen  des  Nervensystems  bei  Polio- 
myelitis ant.   ac.     Nord.   med.  Ark.,  20,   1888. 

—  Quoted   by   v.   Kahlden.      Zentralbl.    f.    allg.   Path,    und   path.   Anat. ,    5, 

1804. 
Robertson  and   Chesley.        Pathology  and   Bacteriology   of   acute   anterior 

poliomyelitis.     Journ.   of  Arner.   Assoc,   55,   igio. 
ROCAS  and  Carles.     Paralvsie  infantile  des  muscles  de  la  paroi  abdominale 

avec  pseudohernie  ventraie.     Arch,  de  med.  des  enf.,   1908. 
ROGER.     Atropine    musculaire    progressive     experimentale.     Ann.     Pasteur, 

1892. 
Roger     and     Damaschino.        Recherches     anatomo-pathologiques     sur     la 

paralysie  spinale  de  l'enfance.      Compt.   rend,   de  la   Soc.   de  Biol.,  3, 

1871. 
Des  alterations   de  la   moelle   epiniere   dans   la   paralysie   spinale   de 

l'enfance   et   dans    l'atrophie    musculaire  progressive.     Rev.    de   med., 

18S1. 
ROMER.      Diskussionsbemerkungen  1m  arztlichen  Verein  zu  Marburg,  Nov.  3, 

igog.     Munch,   med.  AA'ochenschr.,  48,    igog. 

—  Untersuchungen      zur      Atiologie      der      epidemischen     Kinderlahmung. 

Miinch.  med.   AVochenschr.,  49,   igog. 

—  Diskussionsbemerkungen  gelegentlich  der  XIII  Versammlung  siidwest- 

deutsche  Kinderarzte  in  Frankfurt  a.  Main.     Arch  f.  Kinderheilk.,  53. 

—  Weitere  Mitteilungen  liber  experimentelle  Affen-Poliomyelitis.     Miinch. 

med.   Wochenschr. ,  5,    igio. 

—  Diskussionsbemerkungen      gelegentlich     der     4      Tagung      der     Freien 

Vereinigung  fiir  Mikrobiologic,     Berlin,  May  20,  igio.     Zentralbl.  f. 
Bakt.,  47,  Ref. 

—  Epidemiologische    und   atiologische    Studien    iiber    die    spinale    Kinder- 

lahmung.    Verhandl.   des  Deutschen  Kongresses  f.   inn.   Med.,  Wies- 
baden,  1910. 

—  Nachlese  aus  der  experimentellen  Erforschung  der  Poliomyelitis  acuta. 

Med.  Kim.,  28,   1911. 

—  Uber  eine  durch  filtrierbares  virus  bedingte  Meerschweinchenkrankung. 

Zentralbl.  f.  Bakt.,  50,  Ref. 

—  tiber  eine  der  Kinderlahmung  des  Menschen  sehr  ahnliche  Erkrankung 

des  Meerschweins.     Deutsche  med.   Wochenschr.,  26,   191 1. 

—  Uber     den     Erreger     der     Meerschweinchenlahme.       Sitzungsber.      der 

Gesellsch.  z.   Beford.   d.  gesamt.   Naturwissench.     Marburg,  3,   ign. 

—  Experimentelle   Poliomyelitis.      Ergebn.    d.    inn.     Med.  u.    Kinderheilk.. 

1912. 
ROMER  and  JOSEPH.     Beitrag  zur  Natur  des  Virus  der  Epidemischen  Kinder- 
lahmung.    Miinch.   med.   AVochenschr.,   7,    igio. 
Uber   Immunitat  und   Immunisierung  gegen   das  Virus   der  epidemi- 
schen Kinderlahmung.      Ibid.,  10,   igio. 

Spezifisch    wirksames     Serum    gegen     das    Virus    der    epidemischen 

Kinderlahmung.      Ibid.,  11,   igio. 

Beitrage   zur   Prophylaxe    der   epidemischen  Kinderlahmung.     Ibid., 

iS,  1910. 

Zur  Natur  und  Verbreitungsweise  des  Poliomyelitisvirus.      Ibid.,   20, 

igio. 

Noch  einige  Experimente  zur  Poliomyelitisfrage.      Ibid.,  51,   igio. 

Rosenau,    Sheppard,    and    ARROSS.     Poliomyelitis    anterior.     Boston    Med. 

and  Surg.  Journ.,  May  25,   191 1. 
ROSET,    J.       Pequeha    epidemia    de    poliomyelitis    anterior    aguda    infantil. 

Med.  de  los  ninos,  igos,  No.  4. 
ROSSI.     Reprises     chroniques     de     poliomyelite     aigue     de     l'enfance     avec 
apparences  de  myopathic     Rev.   neurol.,    igo5. 

—  Coincidence  chez  un  meme  malade  de  la  paraplegie  cerebrale  infantile 

et  de  la  paralvsie  spinale  infantile.      Nouv.  iconogr.  de  la  Salp.,  igo7. 
ROTH.     Anatomischer      Befund     bei      spinaler     Kinderlahmung.     Virchow's 

Arch.,  58,  1873. 
ROTHMAXW      tiber   die   sckundaren   Degenerationen   nach  Ausschaltung   des 

Sakral-  und  Lendenmarkgrau  durch  Riickenmarksembolie  beim  Hunde. 

Arch,   f    Anat.   u.   Phvsiol.,  iSgg. 


LITERATURE  1 95 

RUMPF.  Beitrage  zur  pathologischen  Anatomie  des  zentralen  Xerven- 
systems.     Arch.  f.  Psych.,   1885. 

Russell,  J.  RISIEX.  The  prognosis  and  treatment  of  acute  anterior  polio- 
myelitis.     Med.    Soc.  Trans.,    1908. 

Sahli.     Zur  Lehre  von  den  spinalen  Lokalisationen.     Deutsch.  Arch.  f.  klin. 

Med.,   1883. 
SALOMON".      Zur   Diagnose    u.    Therapie    einiger    Lahmungsformen    im    kind- 
lichen  Alter.     Jahrb.  f.  Kinderheilk.,  N.F.    1,   1868. 
SANDER.     liber      Riickwirkung      der      spinalen      Kinderlahmung      auf      die 

motorischen    Gebieten    der    Hirnrinde.     Zentralbl.    f.     d.    med.    Wis- 

sensch.,  1875. 
Saunders,    P.  W.     Poliomyelitis   with   extensor  response.     Proc.    Roy.   Soc. 

Med.    (Xeurol.  Sec,  p.  75),  1912. 
SCHAFFER.     Pathologie   u.   pathol.    Anatomie   der   Lyssa.     Zieglers    Beitrage 

z.  Path.  u.  path.  Anat.,  7,   1890. 
SCHAUB,    G.      Zur    Pathologie    der   epidemischen   Kinderlahmung.      Deutsch. 

Zeitschr.  f.    Xervenheilk.,  43,    191 1,    1  and  2. 
Scheltema,  Maxshot,  Travagliaxo,  &c.     Medeeling  over  de  poliomyelitis- 

opeentooping,  1905-06  in  Xederland.     Xed.  Tydschr.  von  Geneesk,  33, 

777- 
Schlesixger.     Verhandl.  der  deutschen  Xervenaxzte.     Ill     Jahresversamm- 

lung,  Wien,  1909. 
SCHMAUS.     Beitrag    zur    Kasuistik    der    akuten    haemorrhagischen    Myelitis, 
Myelitis  bulbi  und  Landryschen  Paralyse.     Zieglers  Beitrage  z.  Path, 
u.  path.  Anat.,  1905. 

—  Akute  Myelitis.     Ergebnisse  von  Lubarsch-Ostertag.     Wiesbaden,   1904. 
SCHMAUS  and  SACKI.     Vorles.  uber  die  path.  Anat.  d.  Riickenmarks.,  1901. 
SCHOXKA.     Uber  die  x-\rt  des  Auftretens  der  infectiosen  Poliomyelitis.     Das 

osterreich.   Sanitatswesen.  Jahrg.  xxi,   1909,  49,  p.  498. 
SchOTTMUller.     Positive  Wassermann  reaction  in  the  blood  of  four  cases 

anterior  poliomyelitis;  not  in  cerebrospinal  fluid.     Arztliche  Verein  in 

Hamburg,  June  25,  1912. 
Schreiber.     La  poliomvelite  epidemique,  Maladie  de   Heine-Medin.     Paris, 

191 1.      G.   Steinheil. 
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spinaler  Kinderlahmung.      Zeitschr.   f.   Medizinalbeamte,  3,  191 1. 
SCHULLER.      Drei  Falle  ooiiomyelitischer  Lahmung  einer  unteren  Extremitat 

mit  positivem  Babinski.     X~eurol.   Zentralbl.,   1905. 
Schultze.     Beitrage     zur    Patholoeie     und     pathologischer     Anatomie     des 

zentralen   Xervensystems,   insbesondere   des  Ruckenmarks.      Virchow's 

Arch.,  68,   1876. 

—  Die    anatomischen    Veranderungen    bei    den    akuten    atrophischen    Lah- 

mungen  der  Erwachsenen.      Ibid.,  73,  1878. 

—  Befund      bei      spinaler     Kinderlahmung    nach     dreijahrigem     Bestehen 

derselben.     Xeurol.  Zentralbl.,  19,  1882. 

—  Tiber  die  Ursache  der  akuten  Poliomyelitis.     Xiederrhein.   Gesellsch.   f. 

Xatur-    und    Heilkunde    in    Bonn,    Xov.     22,     1897.       Deutsche    med. 
Wochenschr.,  5,   1897,  25. 

—  Zur   Atiologie    der   akuten    Poliomyelitis.     Munch,    med.    Wochenschr., 

38,  1S98. 

—  Zur   Anatomie   und   Atiologie   der   akuten   Poliomyelitis.     Munch,    med. 

Wochenschr.,   23,   1904   (Sitzungsbericht). 

—  Zur  pathol.  Anatomie  und  Atiologie  der  akuten  Poliomyelitis.     Zieglers 

Beitrage  z.  Path.  u.  path.  Anat.,  7,  1905. 
SCHWALBE.      Untersuchung   eines    Falles    von    Poliomyelitis   acuta    infantum 

im  Stadium  der  Reparation.     Zieglers  Beitrage  z.  Path.  u.  path.  Anat., 

32,  1Q02. 
Schwartz.     Petersburger  med.  Wochenschr.,  1909. 
Seeligmuller.     Uber  Lahmungen  im  Kindesalter.     Jahrb.    f.    Kinderheilk., 

X.   F.    12,   1878-79. 

—  Spinale  Kinderlahmung.      Handbuch  d.   Kinderkrankh.,  herausgeg.   von 

Gerhardt,  5,   1880. 
SELEXSKY.      Zur  Frage  der  Heine-Medinsche  Krankheit.     Russkij   Wratsch., 

39,  !QJo. 

Seller.  Diskussionsbemerkungen  auf  der  4  Tagung  der  Vereimgung  f. 
Mikrobiologie.      Zentralbl.  f.  Bakt.,  47. 


196  EPIDEMIC    INFANTILE    PARALYSIS 

SHERMAN  and  SPILLER.     Acute  polioencephalomyelitis  in  an  adult.        Phila. 

Med.  Journ.,  igoo. 
Shidler.     The   epidemic  of  spinal   disease   in   Nebraska.     Journ.    of  Amer. 

Med.  Assoc,  1910. 
SlEMERLING.      Zur    pathologischen    Anatomie    der    spinalen    Kinderlahmung. 

Arch.   f.   Psychiatrie,  26,   1894. 

—  Neurol.  Zentralbl.,  10,  1891. 

SINGER.     Uber     experimentelle      Embolien      im     zentralen      Nervensystem. 

Zeitschr.   f.   Heilk.,   18,   1907. 
Sitta.     Autopsie    d'un    cas    de    paralysie    infantile.     XIII.    Internat.    Med. 

Congress,  Paris,  1900. 
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1 1,  1909. 
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AVien,   1908-09.     AVien.  med.  AYochenschr. ,   13,  1910. 
SPILLER.     A    report    of   two    cases    of    paraplegia    occurring   in   variola,    one 

being  a  case  of  anterior  poliomyelitis  in  an  adult.      Brain,    103,   1903. 
STADELMANN.     Beitrag   zur   Path     und.    path.     Anatomie    der   Ruckenmarks- 

erkrankungen.     Deutsch.  Arch.  f.  klin.  Med.,  33,  1883. 
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AArochenschr. ,  34,   1910. 

—  Med.  klinik.,  No.  51. 

Starr.     Epidemic    infantile   paralysis.     Journ.    of   Amer.    Med.    Assoc,    51, 
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—  Acute  Poliomyelitis ;  in  the  Svstem  of  Medicine.     Edited  by  Allbutt  and 

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occurring  in  Victoria.      Intercolonial  Med.  Journ.  of  Australasia,  1908. 
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spinalen    u.    zerebralen    Lahmung.     Jahrb.    f.    Psych,    u.    Neurol.,   32, 

p.   139,   1911. 
Sterne.     Rapports  de  la  paralysie  infantile  avec  la  paralysie  spinale  aigue 

de   l'adulte   et   Fatrophie   musculaire   progressive.     These    de    Nancy, 

1891. 
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in  Oberosterreich.     Med.  klinik.,  44,   1910. 
Strassburger.       Zur    Klinik    der    Bauchmuskellahmung    auf    Grund    eines 

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Zeitschr.  f.  Nervenheilk.,  1906. 
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—  Inoculation   of   nasal   secretion   from   patients   with  acute   poliomyelitis. 

Journ.  of  Amer.  Med.  Assoc,  April  22,  191 1. 
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poliomyelitis.      New  York   Med.  Journ.,   Jan.,    iqio. 
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—  Storungen     der    Sensibilitat    bei    Poliomyelitis.      Deutsch.     Zeitschr.     f. 

Nervenheilk.,  45,  2. 

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Strumpell  and  Barthelmes.     Uber  Pol.  ac  der  Erwachsenen  und  iiber  das 

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LITERATURE  1 97 

TAKAHASHI.      Ein     Fall     akut     entstandener     doppelseitiger     Lahmung     des 

ausseren    Oculomotorius    und    des    Trochlearis.     Klin.    Monatsblatter 

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Aug.  7,  1897. 
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Aug.,  1902. 
Taylor,  Fred.     Transactions  of  Path.  Soc.  London,  30,  p.  197,  1879. 

—  Guy's  Hosp.  Reports,  52,  57,  1895. 

Taylor,  M.     An  epidemic  of   poliomyelitis.     Phila.    Med.  Journ.,   Jan.    29, 

1898. 
Tedeschi.     Paralisi  spinale  infantile  acuta  con  emiatrofia  faciale  ed  atrofia 

del    nervo    ottico.     Atti    dell'    Accademia    di    Sc.    Med.    e    Natur.    in 

Ferrara,  1904. 
Thoinot  and  Masselin.    Contributions  a  l'etude  des  localisations  medullaires 

dans  les  maladies  infectieuses.     Deux  maladies  experimentales  a  type 

spinal.     Rev.   de  med.,   1894,  p.  449. 
THOMAS.      Two   cases   of  acute   ascending  paralysis   with   autopsies.     Journ. 

of  Nerv.  and  Ment.  Dis.,  1897. 
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klin.  Wochenschr.,  No.  2,  1912. 
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med.    Wochenschr.,    19.06. 
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Journ.,  Jan.  27,  1912. 
Treves.     Brain,  32,  p.  285,  1909. 
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mononucleose.     Bull,  et  mem.  Soc.  med.  des  hopit.  de  Paris,  igo2. 
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specimens,    from    a    case    of   acute    anterior   poliomyelitis    in    a    child, 

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30,  1879. 
TWOST.     Etude    de   quelques   microbes   pathogenes   au  point    de  vue    de   la 

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Underwood.     A  treatise  on  the  disorders  of  childhood  and  the  management 
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—  Traite   des   maladies   des   enfants.     Trad,    de    Tanglais   par   Lefebre    de 

Villebrune,  Paris,   1786. 

—  Traite    des   maladies    des    enfants.     Trad,    de    l'anglais    par  Eusebe    de 

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simule  le  syndrome  de  Landry.     Arch.  med.  Exper.,  1893. 
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lung  klin.  Vortrage,   1,   1870. 
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Wendenburg.     Pol.    ant.    ac.    Statistik   der  in  der   Gottinger  medizinischen 
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ig8  EPIDEMIC    INFANTILE    PARALYSIS 

WEST.     Lectures  on  the  diseases  of  infancy  and  childhood.  Second  edition. 

London,  1852,  p.    145. 
WESTERMANN.     Die  in  der  Gottinger  medizinischen   Poliklinik  vom  Jan.    1, 

1877,  bis  Jan.    1,    1901,  beobachteten  Falle  von   Pol.  ant.   ac.      Inaug. 

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WlCKMAN.      Studien     zur    Poliomyelitis    acuta.      Zugleich     ein     Beitrag    zur 

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—  Beitrage     zur     Kenntniss     der     Heine-Medinsche     Krankheit     (Pol.     ac. 

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—  Uber   die   Prognose   der   ak.    Pol.    und  atiol.    verwandte   Erkrankungen. 

Zeitschr.   f.   klin.  Med.,  63,  Heft   1   to  4,  p.  362. 

—  Sur    les    pretendues    relations    entre    la    poliomyelite   ant.    aigue    et    la 

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—  Weitere  Studien  iiber  Pol.   ac.   Ein  Beitrag  zur  Kenntniss  der  Neurono- 

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Neurol,  u.   Psych.,  4,   1910,  Heft   1. 
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WlEKE.  Ercheinungen  der  Poliomyelitis  ant.  ac.  (spinale  Kinderlahmung 
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Williams.  A  case  of  Striimpells  paralysis  (Polioencephalitis)  combined 
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WILLIAMSON.  The  early  changes  in  the  spinal  cord  in  acute  anterior  polio- 
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WlTTEK.  Zur  Behandlung  der  postpoliomyelitischen  schlaffen  Lahmung. 
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WOHLGEMUTH  and  SZECSI.  Zerebrospinal  flussigkeit  in  Pol.  ant.  ac. 
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WOLLENWEBER.  Beobachtungen  iiber  die  epidemisch  auftretende  Spinale 
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WOLLSTEIN.  A  biological  studv  of  the  cerebrospinal  fluid  in  anterior  Polio- 
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Zappert.  Klinische  Studien  iiber  Poliomyelitis.  Jahrb.  f.  Kinderheilk., 
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—  Uber   gehauftes   Auftreten   und    Gelegenheitsursache    der    Poliomyelitis. 

Jahrb.  f.  Kinderheilk.,  53. 
— ■  Bemerkungen  iiber  die  derzeitigen  Poliomyelitis-epidemie  in   Wien  und 
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—  Die     Poliomyelitiserkrankungen     in     Wien     und     Nieder-Osterreich  _  im 

Jahre     1908.      Gesellsch.    f.     inn.     Med.     und    Kinderheilk.     in    Wien, 
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—  Die  epidemie  der  Heine-Medinschen  Krankheit   (Poliomyelitis)  in  Wien 

und'    Nieder-Osterreich    im    Jahre    1908.     AVien.    med.    Wochenschr., 
46,   1909.     Jahrb.    f.    Kinderheilk.,    72,   1910. 

—  Organische    Erkrankungen    des    Nervensystems.       Handb.    der    Kinder- 

heilk. von  Pfaundler  und  Schlossmann.     Second  edition,  iqio. 

—  Verhandlungen    der    82    Versammlung    Deutscher     Naturforscher    und 

Arzte.    Konigsberg,    10 10. 
Zappert,    Leiner    and    v.     Wiesner.      Studien    iiber    die    Heine-Medinsche 
Krankheit   (Poliomyelitis  acuta).      Liepzig  u.  Wien,    191 1. 


Ind 


ex. 

ADULTS,  infantile  paralysis  in,  10 

— ,  prognosis  of  Heine-Medin  disease  bad  in,  20 

Alimentary     tract,     complications     in     prodromal     stage     of     Heine-Medin 

disease,  14 

,  entrance  of  poliomyelitis  virus  by,  101 

America,  North,  epidemics  of  Heine-Medin  disease  in,  140 

Analgesia  in  Heine-Medin  disease,  16 

Andre,  cases  of  infantile  paralysis  in  France,  140 

Animals,  durability  of  poliomyelitis  virus  in,  67,  68 

Antibodies  in  serum  from  cases  of  Heine-Medin  disease,  168-170 

— ■  —  from    experimental    poliomyelitis,    successful    demonstration,     163-166 

— ,  virus  and  serum  containing,  immunization  with,   160 

Antiformin  extracts  in  testing  reaction  in  fixation  of  complement,   163 

Artery,  anterior  spinal,   131 

,  embolism    in    Heine-Medin    disease,    reason    for    rejection    of 

theory,   131,   132  • 

Auerbach,  epidemic  of  infantile  paralysis  in  Germany,  138 
Australia,  epidemics  of  Heine-Medin  disease  in,  141 
Austria,  epidemic  of  Heine-Medin  disease  in,  138 

BACILLUS  COLI,  intravenous  infection  in  rabbits  producing  paralysis,  30 
Bacteriological  research  in  Heine-Medin  disease,  26 

,  negative,  27 

Badham,  case  of  infantile  paralysis,  6 

Batten,  F.  E.,  cases  of  infantile  paralysis,  13Q 

Beclere,  cases  of  infantile  paralysis  in  France,  140 

Bergenholtz,  epidemic  of  infantile  paralysis  in  Sweden,  137 

Blood-vessels,  infiltration  about,  in  poliomyelitis,  70, 

Bonhoff,  discovery  of  bodies  in  nuclei  of  glia  cells  in  case  of  poliomyelitis, 

— ,  injection  of  poliomyelitis  virus  into  rabbits,  73 
Borna's  disease  in  horses,   133 

— ■  —  in  relation  to  Heine-Medin  disease,  28,  128,  i2Q 
— ■  — ,  nature  of,  28 
— -  — ,  path  of  infection,   134 
Boston,  epidemic  of  infantile  paralysis  in,  140 

Brain,  abscess  of,  causing  symptoms  of  cerebral  paralysis  in  monkeys,  53,  54 
— ,  microscopic   changes  in   poliomyelitis   of  monkeys   and   man   compared, 
106,   122-124 

,  similar,   103-106 

Briegleb,  cases  of  infantile  paralysis  in  Germany,  138 

Broth-culture  methods  in  Heine-Medin  disease,  25 

Briick,  cases  of  infantile  paralysis,  6 

Buccelli,  cases  of  infantile  paralysis  in  Genoa,   140 

Biilow-Hansen,  epidemic  of  infantile  paralysis  in  Norway,  137 

Bull,  epidemic  of  infantile  paralysis,   136,   137 

Buzzard,  E.  F.,  cases  of  infantile  paralysis,  13Q 

CARBOLIC  ACID  influence  on  poliomyelitis  virus,  67 

Caverley  and  Macphail,  epidemic  of  infantile  paralysis  in  Vermont,  140 

Cerebrospinal  fluid,  examination  in  Heine-Medin  disease,  26,  27 

from  monkeys  after  recovery  from  infection,  antibodies  in,   166 

,  human,  alleged  production  of  poliomyelitis  in  monkeys  from,  80,  81 


200  EPIDEMIC   INFANTILE  PARALYSIS 

Cerevesato,  cases  of  infantile  paralysis  in  Italy,  140 

Charcot,  changes  in  spinal  cord  in  epidemic  infantile  paralysis,  4,  5 

Charcot  and  Joffroy,  pathology  of  infantile  paralysis   (discovery  of  loss  of 

ganglion  cells  of  spinal  cord),  go,  gi 
Chemicals,  effects  on  poliomyelitis  virus,  67 
Clark,  Lockhart,  pathology  of  infantile  paralysis,  go 
Cocci,  era  of,  in  history  of  Heine-Medin  disease,  24 
Colmer,  early  cases  of  infantile  paralysis,  136 
Complement-fixation  in  experimental  poliomyelitis,  162 

Connecticut,  epidemic  of  infantile  paralysis  (Heine-Medin  disease)  in,  141 
Convulsions  accompanying  cerebral  paralysis  in  monkeys.  53 
Cordier,  cases  of  infantile  paralysis  in  France,  140 
Cornil,  pathology  of  infantile  paralysis,  8g,  go 
Cornwall,  see  Devon  and.  Cornwall 
Cuba,  epidemic  of  Heine-Medin  disease  in,  141 

Dentition,  troubles  of,  in  relation  to  Heine-Medin  disease,  176 

Devon   and   Cornwall,   epidemic   of   poliomyelitis  in,    130 

Diarrhoea  in  poliomyelitis  in  monkeys,  54,  55,  56 

Diplococcus  from  case  of  poliomyelitis  causing  paralysis  in  rabbits,  78 

Disinfectant  measures  in  Heine-Medin  disease,  176 

Disinfectants,  behaviour  of  poliomyelitis  virus  towards,  67 

Drying,  resistance  of  poliomyelitis  virus  to,  66 

Duchenne,  change  of  faradic  reactions  of  muscles  in  infantile  paralysis,  10 

Dust,  experimental  production  of  poliomyelitis  in  monkeys  by,  148 

Eckert,  second  attack  of  Heine-Medin  disease,  I4g 
Eichelberg,  epidemic  of  Heine-Medin  disease  in  Hanover,  138 
Encephalitis  and  infantile  paralysis,  connection  between,  1 

—  due  to  Heine-Medin  disease,  serum  diagnosis,  ig 
— ,  pontinea,  11 

England,    compulsory    notification    of    poliomyelitis    (Heine-Medin    disease) 

in  (ign),  i3g 
— ,  epidemics  of  Heine-Medin  disease  in,   i3g 
Epidemics  of  Heine-Medin  disease,  136-148 

,  accumulation  of  negative  results  as  to  aetiology,  25 

Eshner,  second  attack  of  Heine-Medin  disease,  149 

FabriS,  cases  of  infantile  paralysis  in  Italy,  140 

Faradic  reactions  of  muscles  in  infantile  paralysis,  changes  in,  10 

Filtration  of  poliomyelitis  virus,  62,  133 

,  best  methods  employed,   133 

Flexner,  attempt  to  cultivate  virus  of  Heine-Medin  disease,  29,  30 

— ,  epidemics  of  infantile  paralysis  (Heine-Medin  disease)  in  United  States, 

— ,  nystagmus  accompanying  cerebral  paralysis  in  monkeys,  53 

Flexner    and    Clark,    antibodies    in    cerebrospinal    fluid    in    poliomyelitis    of 

monkevs,  166 
Flexner  and  Lewis,  attempts  to  determine  point  of  entrance  of  poliomyelitis 

virus,   101 

■ ,  convulsions  accompanying  cerebral  paralysis  in  monkeys,  53 

,   demonstration  of  antibodies  in  antipoliomyelitic  serum,  165 

1   distribution    of    poliomyelitis    virus    in    organs    of    monkeys,    96,    97, 

98,  QO  ,.,.-.," 

—  - — ,  effect  of  high  temperatures  on  poliomyelitis  virus.  66 

passing  poliomyelitis  virus  through  animals,  68,  69 

— perhydrol  on  poliomyelitis  virus,  67 

—  — ,  facial  paralysis  in  poliomyelitis  of  monkeys,  50,  51 
,  filtration  of  poliomyelitis  virus,  62 

,  immunity  of  monkeys  to  poliomyelitis  after  first  attack,   153 

,  inoculation  of  monkeys  with  virus  of  poliomyelitis,  43,  44,  45 

,  poliomyelitis  virus  in  mesenteric  glands  in  child,  95 

,  resistance  of  poliomyelitis  virus  to  drying,  66 

,  serum-therapy  in  Heine-Medin  disease,  172 

Fbrssner  and  Sjovall,  pathology  and  pathogenesis  of  Heine-Medin  disease, 

94 
Forster,  O.,  epidemic  of  Heine-Medin  disease  in  Schleswig,  138 
Formalin,  effect  on  emulsion  of  poliomyelitis  virus,  67 


INDEX  20I 

Foulerton,  A.  G.  R.,  Pasteur,  W.,  and  MacCormac,  H.,  results  of  injection 

of  cerebrospinal  fluid  into  rabbits,  70 
France,  epidemics  of  Heine-Medin  disease  in,  139,  140 
Frankenau  (Hesse),  spread  of  Heine-Medin  disease  at,  146 

Gastrointestinal  route,  portal  of  entry  of  poliomyelitis  virus  by,  135 

—  symptoms  in  poliomyelitis  of  monkeys,  54 
Genoa,  cases  of  infantile  paralysis  in,   140 
Germany,  epidemics  of  Heine-Medin  disease  in,  138 

Giersvold,  discovery  of  cocci  in  epidemics  of  Heine-Medin  disease,  24 
Glia  cells,  discovery  of  bodies  in  nuclei  of,  in  case  of  poliomyelitis,  20, 
Glycerine,  preservation  of  poliomyelitis  virus  in,  64 
— ,  resistance  of  poliomyelitis  virus  to,  63 

Goldscheider,    microscopical     and     cultural     investigation    in     Heine-Medin 
disease,  24 

—  pathology  of  infantile  paralysis,  Q3 

Guinon  and  Rist,  cases  of  Heine-Medin  disease  in  France,  140 

Hemolytic  system  in  testing  reaction  in  fixation  of  complement,  163 
Hanover,  epidemic  of  Heine-Medin  disease  in,  138 
Harbitz,  epidemic  of  infantile  paralysis  in  Norway,  137 
Harbitz  and  Scheel,  immunity  to  Heine-Medin  disease,  i4g 

,  pathology  and  pathogenesis  of  Heine-Medin  disease,  Q4 

v.  Heine,  J.,  biographical  sketch  of,  g 

— ,  name  "  spinal  infantile  paralysis  "  adopted  by,   1 

— ,  pathology  of  infantile  paralysis,  87 

— ,  reasons  for  assuming  lesion  of  spinal  cord  in  infantile  paralysis,  88,  8g 

— ,  stages  of  infantile  paralysis  observed  by,  7 

Heine-Medin  disease,  adoption  of  term  by  Wickman,  2 

—  — ,  antibodies  from  serum  in  case's  of,  168-170 
,  atypical  (marantic)  forms,  131 

~j  bacteriological  research  by  author,  26 

-,  Borna's  disease  in  relation  to,  28,  128,  i2g 

,  carriers  of,  146-148,  176 

•  — 3  communication  with  must  be  cut  off,  175 

—  — ,  cerebral  forms,   170 

,  contagiousness,  proof  of,  144-146 

,  dentition  in  relation  to,  176 

,  disinfectant  measures  in,  176 

j  economic  and  humane  reasons  for  combating,  174,  175 

,  epidemics,  25 

,  age  and  sex  predisposition,  142,  143,  144 

■  — ,  large,  origin  of,   141 

,  season  of,   142,   143 

,  epidemiology,    136-148 

,  era  of  cocci  in  history  of,  24 

,  etiology,  22-86 

,  accumulation  of  negative  results,  25 

,  historical  account,  6-13 

retrospect,  3 

,  immunity  to,  I4g-i62 

,  clinical  and  epidemiological  experience,   149 

,  immunization  against,   i4g-i62 

3  incubation  period,   ,3 

,  Landry's  paralysis  in  relation  to,  128 

,  lesion,  primarily  vascular  or  perivascular,  130 

,  microscopical  and  cultural  investigation,  24 

,  occupation  in  relation  to  prevalence,  147 

,  pathogenesis,   129-135 

—  — ■  — ,  problems  in,  94 

3  pathology  and  pathogenesis,  87-135 

polyneuritis  in  relation  to,   128 

•  ■ — ■ ,  in  adults,  128 

,  primary  affection  of  ganglion  cells  may  occur,  130 

,  prodromal,  13 

,  prognosis,  ig 

,  prophylaxis,  personal,   175 


202  EPIDEMIC   INFANTILE  PARALYSIS 

Heine-Medin  disease,  rabies  in  relation  to,  128 
,   serum  diagnosis  of,   166-171 

—  — ,   serum-therapy,    171 
,  results,  172,  173 

,   spread  of,  along  lines  of  traffic,   137 

,   stage  of  paralysis  in,   14-19 

,  State  regulation,  177 

,  strict  precautions  necessary,  178 

,  symptomatology  in  man,  13-21 

symptoms,  clinical,  difficulty  in  explaining,  131 

,  prodromal,   13 

,  treatment  by  drugs,  173 

,  symptomatic,  174 

,  use  of  broth-cultures  in,  25 

,  see  also  Paralysis,  infantile;  Poliomyelitis 

Herpes  zoster  and  poliomyelitis,  etiology  of,  170,  171 
Hesse-Xassau,  epidemic  of  Heine-Medin  disease  in,  26,  34,  13b 
Hoffmann,  cases  of  infantile  paralysis  in  Germany,  138 
— ,  epidemic  of  Heine-Medin  disease  in  Germany,   138 
Holland,  cases  of  Heine-Medin  disease  in,   139 
Horses,  Borna's  disease  in,  28 ;  see  also  Bo  ma's  disease 
Hydrogen,  peroxide  of,  effect  on  poliomyelitis  virus,  67 
Hydrophobia,  intracellular  bodies  in  ganglion  cells  in,  28 
— ,  method  of  transmission  from  animal  to  animal,  33 

—  and  poliomyelitis,  similarity  of  histological  changes  in,  33 
Hypersensitiveness,   specific  negative  results  in  experimental  poliomyelitis, 

163 

Immunity  and  immunization  in  Heine-Medin  disease,  149-162 
Intracellular  bodies  in  ganglion  cells  in  hydrophobia,  28 
Italy,  epidemics  of  Heine-Medin  disease  in,  14c 

JORG,  case  of  infantile  paralysis,  6 

Joest,  Borna's  disease  in  horses,  28,  133,  134 

Joest  and  Degen,  Borna's  disease  in  horses,  128,  129 

Jogichess,   grouped  cases  of  infantile  paralysis  in  St.   Petersburg   (1909-10), 

140 
Joseph,  injection  of  poliomyelitis  virus  into  rabbits,  75 

Kennedy,  cases  of  "  temporary  paralysis"  described  by,  10 
Key  and  Retzius,  distribution  of  poliomyelitis  in  organs  of  monkeys,  99 
Kidneys,  inflammation,  in  poliomyelitis  in  man,  103 
Kraus,  influence  of  carbolic  acid  on  poliomyelitis  virus,  67 
— ,  injection  of  poliomyelitis  virus  into  rabbits,  74 
— ,  serum  therapy  in  Heine-Medin  disease,  172 

Krause  and  Meinicke,  attempts  to  determine  point  of  entrance  of  polio- 
myelitis virus,   101 

,  attempts  to  produce  poliomyelitis  in  rabbits,  70,  73,  74,  75,  77-86 

,  immunity  of  monkeys  to  poliomyelitis  after  first  attack,  154 

Landry's  paralysis  and  infantile  paralysis,  similarity  or  identity  of  patho- 
logical processes,  11,  17 

Landsteiner  and  Levaditi,  attempts  to  determine  point  of  entrance  of  polio- 
myelitis virus,   101 

,   demonstration  of  antibodies  in  antipoliomyelitic  serum,   165 

,   durability  of  poliomyelitis  virus  in  animals,  68 

,   effect  of  chemicals  upon  poliomyelitis  virus,  67 

low  temperatures  on  poliomyelitis  virus,  65 

potassium  permanganate  and  peroxide  of  hydrogen  on  polio- 
myelitis virus,  67 

,  filtration  of  poliomyelitis  virus,  62 

,  immunity  of  monkeys  to  poliomyelitis  after  first  attack,  153 

,  inoculation  of  monkeys  with  poliomyelitis  virus,  43,  44 

,  pathogenesis  of  Heine-Medin  disease,   130 

,  resistance  of  poliomyelitis  virus  to  drying,  66 

— to  glvcerine,  63 


INDEX  203 

Landsteiner   and   Popper,    experimental   transmission   of   poliomyelitis   from 

human  subject  to  monkeys,  31,  32 
Leegaard,  epidemics  of  Heine-Medin  disease  in  Norway,  137 
Leiner    and    von    AViesner,    attempts    to    determine    point    of    entrance    of 

poliomyelitis  virus,   101,   102 

,   demonstration  of  antibodies  in  antipoliomyelitic  serum,   165 

,  durability  of  poliomyelitis  virus  in  animals,  68 

,  effect  of  high  temperatures  on  poliomyelitis  virus,  66 

passing  poliomyelitis  virus  through  animals,  68 

,   facial  paralysis  in  poliomyelitis  of  monkeys,  50 

,  filtration  of  poliomyelitis  virus,  62 

,   immunity  of  monkeys  to  poliomyelitis  after  first  attack,   153 

,  inoculation  methods  of  poliomyelitis  virus,  99,   100 

—  — -  —    of  monkeys  with  poliomyelitis  virus,  43,  44,  45 

,  marasmic  forms  of  iDoliomyelitis  in  monkeys,  56 

,  resistance  of  poliomyelitis  virus  to  drying,  66 

,  serum  therapy  in  Heine-Medin  disease,  172 

Lentz    and   Huntemiiller,    injection   of   poliomyelitis   virus   into    rabbits,    75, 

79,  82 

Levaditi,  attempt  to  cultivate  virus  of  Heine-Medin  disease,  29,  30 

— ,  effect  of  low  temperatures  on  poliomyelitis  virus,  65,  66 

Levaditi  and  Landsteiner,  serum  therapy  in  Heine-Medin  disease,   172 

Levaditi  and  Stanesco,  facial  paralysis  in  poliomyelitis  of  monkeys,  50,  51 

,  relapse  in  poliomyelitis  of  monkeys,  5g 

Lorenzelli,  cases  of  infantile  paralysis  in  Parma,   140 
Lumbar  puncture  in  Heine-Medin  disease,   174 

Lymph   channels   in   central   nervous   system,    spread   of   poliomyelitis   virus 
along,  133,  134 

MacCormac,  H.,  Foulerton,  A.   G.   R.,  and  Pasteur,  W.,  results  of  injection 

of  cerebrospinal  fluid  into  rabbits,  70 
Man,  demonstration  of  poliomyelitis  virus  in  different  organs  in,  95 
— ,  pathological   changes   found   in    experimental   poliomyelitis   in   monkeys 

compared  with  those  in,  102 
— ,  symptomatology  of  Heine-Medin  disease  in,   13-21 
Marasmic  forms  of  poliomyelitis  in  monkeys,   56 
Marks,  H.  K.,  attempts  to  produce  poliomyelitis  in  rabbits,  85 
Massachusetts,  epidemic  of  infantile  paralysis  (Heine-Medin  disease)  in,   141 
Medin,  cerebral  forms  of  Heine-Medin  disease,  170 
— ,  epidemics  of  infantile  paralysis  in  Sweden,   137 
— ,  proof   of    connection   between   infantile   paralysis   and    certain    forms    of 

encephalitis,   1 
Meningitis,  epidemic,  similarity  of  epidemic  poliomyelitis  to,  97 
Meningo-myelo-encephalitis,  disseminated,  93 

Menthol  as  mouth-wash  in  prophylaxis  of  Heine-Medin  disease,   175 
- — ■    oil,  effect  on  poliomyelitis  virus,  67 
Mesenteric  glands  in  child,  poliomyelitis  virus  in,  gs 

,  in  monkeys,  poliomyelitis  virus  in,  98 

Micro-organisms,  attempts  to  produce  myelitis  by  experimental  injection,  30 
Mdbius  and  Sanger,  cases  of  infantile  paralysis  in  Germany,  138 
Monckeberg,  pathology  of  infantile  paralysis,  92 
Monkeys,     intracerebral     injection     of    poliomyelitis     virus     into     monkeys. 

technique,  33 
— ,  poliomvelitis    in,    alleged    production    from   human    cerebrospinal    fluid, 

80,  8;  _ 

,  clinical  history,  43-61 

■ — -  — ,   demonstration  in  different  organs,  95,  96 

— -  — ,  pathological  changes  compared  with  those  in  man,  102 

virus  passed  through,  injected  into  rabbits,  72 

— ,  results  of  injection  of  poliomyelitis  into  rabbits,  tested  on,  76,  77 

— ,   susceptibility  to  poliomyelitis  virus,  42 

— ,  transmission  of  poliomyelitis  from  human  subject  to,  31,  32 

from  one  to  another,  33 

— ,  use  of  animals  other  than,  for  experiment,  69-86 

Mouth,  cleansing  of,  prophylactic  against  Heine-Medin  disease,  175-176 
Miiller,  contagiousness  of  Heine-Medin  disease,  146 

Muller,    E.,    economic    and    humane    reasons    for    combating    Heine-Medin 
disease,  174,  175 


204  EPIDEMIC  INFANTILE  PARALYSIS 

Mliller,  E.,  epidemic  of  Heine-Medin  disease  in  Hesse-Nassau,  138 

— j   season  of  epidemics  of  Heine-Medin  disease,  142,  143 

— ,   symptomatology  of  Heine-Medin  disease  in  man,   13,   14 

Muscles,  faradic  reactions  in  infantile  paralysis,  changes  in,   10 

Myelitis,  certain  forms  identified  with  poliomyelitis,  g4 

— ,  experimental  attempts  to  produce  lesions  of,  comparable  to  Heine- 
Medin  disease,  30 

Myelo-encephalitis  disseminated,  infiltrative,  Borna's  disease  in  horses  same 
as,  28 

Nannestad,  epidemic  of  Heine-Medin  disease  in  Norway,   137 

Nebraska,  epidemic  of  infantile  paralysis  (Heine-Medin  disease)  in,   141 

Negri,  intracellular  bodies  in  ganglion  cells  in  hydrophobia,  28 

Nerves,  direct  injection  of  poliomyelitis  virus  into,  100 

Nervous     system,     complications     in     prodromal      stage     of     Heine-Medin 

disease,  14 
,  central,    inflammatory   process   in,    symptoms   of   poliomyelitis   acuta 

due  to,  03 
,  persistence    of    poliomyelitis    virus    in    other    regions    longer    than 

in,  68 

,  spread  of  poliomyelitis  virus  within,  132 

■ ,  along  lymph  channels,   133,   134 

Netter,   epidemic  of  Heine-Medin  disease  in  and  about  Paris   (igog),   140 

— ,  facial  paralysis  in  poliomyelitis  of  monkeys,  50 

Netter  and  Levaditi,  antibodies  in  serum  from  cases  of  Heine-Medin  disease, 

168 
Neuritis,  certain  forms  of  grouped  with  poliomyelitis,   11 
Neuronophagy  of  spinal  ganglion  cells  in  poliomyelitis,   115-121,   130 
New  Jersey,  epidemic  of  infantile  paralysis  (Heine-Medin  disease)  in,  141 
New  York,  epidemics  of  infantile  paralysis   (Heine-Medin  disease)  in,   140, 

J4i  .... 

Nobecourt  and  Darre,  serum  therapy  in  Heine-Medin  disease,  173 
Norway,  epidemics  of  Heine-Medin  "disease  in,  136,  137,  141 
Nystagmus  accompanying  cerebral  paralysis  in  monkeys,  53 

Oppexheim,  ''•'  encephalitis  pontinea,"  11 

Osgood    and    Lukas,    persistence    of    poliomyelitis    virus    in    pharynx    after 

disappearance  from  nervous  system,  68 
Oxholm,  outbreak  of  infantile  paralysis  in  Norway,  137 

Pain  and  tenderness  in  prodromal  stage  of  Heine-Medin  disease.    14 
Painter,  epidemic  of  infantile  paralysis  in  Boston,   140 
Paralysis  (abortive)  in  Heine-Medin  disease,  14 

—  (bulbar  and  cerebral)  in  poliomyelitis  of  monkeys,  40,  53 

-in  poliomyelitis  of  monkeys  accompanied  by  convulsions,  53 

accompanied  by  nystagmus,  53 

—  (bulbar  and  pontine)  in  Heine-Medin  disease,  18 

—  (cerebral),  certain  kinds  of,  grouped  with  spinal  infantile  palsies,  11 
-in  Heine-Medin  disease,  18 

— ■  —  in  monkeys,  due  to  brain  abscess,  53,  54 

—  during  dentition,  22 

— ,  experimental  production  in  animals,  30 

—  (facial)  in  polionryelitis  of  monkeys,  50,  31 

—  in  Heine-Medin  disease,  recovery  from,  20 
,  types  of,   14-ig 

—  in  poliomyelitis  of  monkeys,  45 

,  confers  immunity  to  second  attack,   153,   154 

— ,   similar  to  that  occurring  in  man,  46 

—  in  rabbits  following  infection  with  streptococci,  78 
,  with  diplococcus  from  case  of  poliomyelitis,  78 

—  (infantile),  acute  and  chronic  stages,  7,  8 
,  and  encephalitis,  connection  between,  1 

,  and    Landry's    disease,    similarity    or    identity    of    pathological    pro- 
cesses,  11,   17 
,  changes  in  faradic  reactions  of  muscles  in,  10 

—  - — ,  epidemic  and  sporadic,  identity  proved  by  serum  test,  21 
— ,  first  adoption  of  term,  1 


INDEX  205 

Paralysis  (infantile),  first  occurrence  in  epidemics,  136 
— ■  — ,   "  idiopathic  "  or  "  essential, ;)  1,  23 
,   in  adults,  10 

—  - — ,   sporadic,  20 

,  see  also  Heine-MecLin  disease,  Poliomyelitis 

—  of  left  hind  limb  in  poliomyelitis  of  monkeys,  58 

—  (Landry's)  identity  with  poliomyelitis,  Q4 

,  in  relation  to  Heine-Medin  disease,   128 

— ■  — ,  poliomyelitis  acutissima  in  case  of,  02 

■ —   (spinal)  in  Heine-Medin  disease,   15 

in  poliomyelitis  of  monkeys,  47,  60 

,  infantile,  date  of  adoption  of  term,  1 

,  reasons  for  retention  of  name,  2 

Paris,  epidemic  of  Heine-Medin  disease  in  and  about  (ipog),  140 

Pasteur,     L.,     method    of     transmission    of     hydrophobia     from     animal     to 

animal,  33 
— ,  effect  of  passing  virus  of  rabies  through  rabbits,  6q 
Pasteur,  W.,  outbreak  of  infantile  paralysis  in  one  family,  i3g 
Pasteur,  W.,  Foulerton,  A.  G.  R.,  and  MacCormac,  H.  ,  results  of  injection 

of  cerebrospinal  fluid  into  rabbits,  70 
Perhydrol,  effect  on  poliomyelitis  virus,  67 
Pes  cavus  following  Heine-Medin  disease,  16,  17 
Pharynx,    persistence    of    poliomyelitis    virus    in,    after    disappearance    from 

central  nervous  system,  68 
Pia  mater,   cerebral   and  spinal,   microscopic  changes  in  monkey  and  man, 

compared,   107-111 
Pieper,  epidemic  of  Heine-Medin  disease  in  Pomerania,   138 
Pieraccini,  cases  of  infantile  paralysis  in  Italy,   140 
Platou,  epidemic  of  Heine-Medin  disease  in  Xorway,  137 
Poliomyelitis  acuta  in  monkeys,  47 

,  symptoms  of,  cause,  93 

— ■  acutissima,   18 

— •  — -in  case  of  Landry's  paralysis,  02 

-in  monkeys,  46 

—  and  herpes  zoster,  etiology  of,   170,  171 

— ■  and  hydrophobia,  similiarity  of  histological  changes  in,  33 

—  and    rabies,     biological     connection    between,     from    point     of    view    of 

immunity  wanting,  162 

—  anterior  acuta,  date  of  adoption  of  term,   1 
— ,   certain  forms  of  neuritis  grouped  with,  n 

— ,  clinical    and    -post-mortem     records    of    cases    from     which     virus     was 

obtained  for  experiments,  34-42 
— ,  compulsory  notification  in  England  (ign),   130 
— ,   diplococcus  from  case  of  causing  paralysis  in  rabbits,  78 
— ,  discovery  of  bodies  in  nuclei  of  glia  ceils  in  case  of,  2Q 
— ,    (epidemic),    first    adoption    of    term,    1 

,  in  Hesse-Nassau  (igog),  34 

— ■  — ,   similarity  to  epidemic  meningitis,  07 

—  in  adults  in  relation  to  Heine-Medin  disease,   12S 

—  in  monkeys,  abortive  forms,  54,  55 

,  alleged  production  from  human  cerebrospinal  fluid,  80,  81 

— ■  — ,  antibodies  in  serum  from,  successful  demonstration,  163-166,  168 

,  attempts  at  re-infection,   151 

— ■  — ,  clinical  history,  43-61 

— ■  — ,  experimental,  fixation  of  complement  in,  162 

,  gastro-intestinal  symptoms,  54 

-,  immunity  after  first  attack,    151-153 

,  conferred  if  paralysis  has  been  present,  153,  154 

,  incubation  period,  43 

,  longer  when  filtered  virus  used,  63 

,  marasmic  forms,  56 

,  paralysis  in,  47,  4g,  50,  51,  58 

,  recovery  from,   57,   50 

,  pathological  changes  compared  with  those  in  man,   102 

,  macroscopic,  103 

,  prodromal  symptoms,  44 

,  prognosis  bad,  60,  61 

,  recovery  from  acute  stage,  57 


206  EPIDEMIC  INFANTILE  PARALYSIS 

Poliomyelitis  in  monkeys,  relapses,  59 

,  specific  hypersensitiveness  in,  negative  results,  163 

,  stage  of  paralysis,  45 

,  of  repair,   125 

■  — ,  final,   127 

,  time  of  onset  of  lesions,  127 

■ ,  transmission,  by  saliva  and  dust,   148 

— ,  infiltration  around  blood-vessels  in,  79 

■ — ,  Landry's  paralysis  and  certain  forms  of  myelitis  identified  with.  g4 

— ,  transmission  from  monkey  to  monkey,  33 

to  monkeys  from  human  subjects,  31,  32 

— ,  see  also  Heine-Medin  disease;  Paralysis,  infantile 

—  virus,  behaviour  towards  disinfectants,  67 
,  cultures  of,  29 

j  demonstration  in  different  organs  in  man,  95 

in  monkeys,  95,  96 

,   difference  from  that  of  rabies,  66 

,   distribution  and  spread  within  organism,  94 

,   dry,  protective  inoculation  with,   156 

,   durability  in  animals,  67,  68 

,  effect  of  "  change  of  host,"  69 

of  low  and  high  temperatures  on,  65,  66 

of  passing  through  animals,  68 

,  "  exaltation"  of,  69,  71 

—  — ,  filtered  and  unfiltered,  difference  in  virulence  between,  62 
,  filtration  of,  62 

,  glandular  distribution  in  monkeys,.  98 

— -  — ,  immunization  by  small  doses,  157 

methods,  156-162 

with  during  incubation  period,   162 

when  attenuated  or  killed  by  chemical  means,  158 

when  heated,  159 

in  mesenteric  glands  in  child,  95 

,  injection  into  rabbits,  results,  70,  71,  73-86 

,  results  tested  by  simultaneous  injection  into  monkeys,  76,  77 

,  inoculation,  by  direct  injection  into  nerves,   100 

,  intracerebral,   99 

into  monkeys,  technique,  33 

,  intravenous,  100,  133 

— ,  subcutaneous,  100 

,  nature  of,  61-69 

passed  through  monkeys  injected  into  rabbits,  72 

,  persistence  of,   176,  177 

,  point  of  attack,  i2g 

— ■  — ,  portal  of  entry,  101,  134,  135 

attempts  to  determine,   101 

— -  — ■ by  gastro-intestinal  route,  135 

,  preservation  in  glycerine,  64 

,  resistance  to  drying,  66 

—  to  glycerine,  63 

after  passing  through  animals,  63 

,  route  to  spinal  cord,  133 

,  similarity  to  that  of  rabies,  63 

—  — 5  spread  within  central  nervous  system,  132 
,  susceptibility  of  monkeys  to,  42 

transmitted  through  the  best  filters,  133 

used  in  experiments,  source  of,  34-42 

.    and  serum  containing  antibodies,  immunization  with,   160 

Polyneuritis  in  relation  to  Heine-Medin  disease,  128 

Pomerania,  epidemic  of  Heine-Medin  disease  in,   138 

Potassium  permanganate,  effect  on  poliomyelitis  virus,  67 

Potpeschnigg,    diplococcus    from    case    of    poliomyelitis    causing    paralysis 

in  rabbits,  78 
— ,  epidemic  of  Heine-Medin  disease  in  Austria,  139 
Prevertebral  glands  in  monkey,  poliomyelitis  virus  in,  98 
Prevost  and  Vulpian,  pathology  of  infantile  paralysis,  90 
Prognosis  in  Heine-Medin  disease,  10 
,  bad  in  adults  compared  with  children,  20 

—  in  poliomyelitis  of  monkeys,  bad,  60,  61 


INDEX  207 

Rabbits,  attempts  to  produce  myelitic  lesions  in,  experimentally,  30 

— ,  effect  of  passing  virus  of  rabies  through,  69 

— ,  injection  of  cerebrospinal  fluid  into,  results,  70,  71 

poliomyelitis  virus  into,  after  passing  through  monkeys,  72 

,  results,  70,  71,  73-86 

compared  with  those  in  control  monkeys,  76,  tj 

— ,  paralysis  in,  caused  by  infection  with  diplococcus  from  case  of  polio- 
myelitis, 78 

— ,  paralysis  in,  caused  by  infection  with  streptococci,  78 

Rabies  and  poliomyelitis,  biological  connection  between,  from  point  of 
view  of  immunity  wanting,  102 

— ,  in  relation  to  Heine-Medin  disease,   128 

— ,  virus  of,  and  poliomyelitis  virus,  63,  66 

,  effect  of,  passing  through  rabbits,  6g 

Reece,  epidemic  of  poliomyelitis  in  Devon  and  Cornwall,   139 

Respiratory  tract,  complications  in  prodromal  stage  of  Heine-Medin 
disease,  14 

,  lower,  entrance  of  poliomyelitis  virus  by,  101 

Rissler,  pathology  of  infantile  paralysis,  02 

Roger  and  Damaschino,  pathology  of  infantile  paralysis,  qi 

Romer,  P.  H.,  bacteriological  research  in  Heine-Medin  disease,  26 

,  injection  of  poliomyelitis  virus  into  rabbits,  71 

Russia,  cases  of  Heine-Medin  disease  in,  140 

St.  Petersburg,  cases  of  infantile  paralysis  in  (igog-io),  140 

Saliva,  experimental  production  of  poliomyelitis  in  monkeys  by  injections 
of,  148 

San  Francisco,  epidemic  of  infantile  paralysis  in,  140 

Scandinavia  (see  Norway,  Sweden) 

Schleswig,  epidemic  of  Heine-Medin  disease  in,   138 

School  infection  of  Heine-Medin  disease,  146 

Schultze,  discovery  of  cocci  in  Heine-Medin  disease,  24 

Scoliosis,  following  Heine-Medin  disease,  16,  17 

Selter,  infection  of  rabbits  with  streptococci  causing  paralysis,  78 

Serum  and  virus  containing  antibodies,  immunization  with,  160 

—    (antipoliomyelitic),  specific  antibodies  present  in,   163-166,  168 

Serum-diagnosis  of  encephalitis  due  to  Heine-Medin  disease,   ig 

■    of  Heine-Medin  disease,  166-171 

— •,  of  identity  of  infantile  paralysis  in  sporadic  and  epidemic  forms,  21 

Serum-therapy    of    Heine-Medin    disease,    171 

,  results,  172,  173 

Siemerling  and  Dauber,  microscopical  and  cultural  investigation  in  Heine- 
Medin  disease^  24 

Simonini,  cases  of  infantile  paralysis  in  Italy,  140 

Spain,  epidemics  of  Heine-Medin  disease  in,  140 

Spinal  cord,  anterior  horns,  vulnerability  in  Heine-Medin  disease,   131 

■ ,  blood-vessels  of,  infiltration,  in  poliomyelitis,   111,   112 

,  ganglion  cells,  alterations  in  poliomyelitis  of  monkeys  and  man,  11^ 

■ ,  hypersemia,    haemorrhages    and    degeneration    in    Heine-Medin 

disease,  131 

,  primary  lesion  of,  occurring  in  Heine-Medin  disease,  130 

-,  implication    in    infantile    paralysis,    Heine's   reasons    for   postulating, 

88,  bg 

,  loss  of  ganglion  cells  in  infantile  paralysis,  go 

,  macroscopic  changes  in  poliomyelitis  of  monkeys  and  man,  similar, 

103-106 

-,  microscopic  changes  in  poliomyelitis  of  monkeys  and  man  com- 
pared, 105,  106,  107,  111-122 

,  route  of  poliomyelitis  virus  to,   133 

Spleen,  swollen,  in  poliomyelitis  in  man,  103 

Stephens,  negative  etiological  results  in  Heine-Medin  disease,  25 

Sterne,  second  attacks  of  Heine-Medin  disease,  150 

Strauss,  alterations  in  ganglion  ceils  in  poliomyelitis.   115 

Streptococci,  infection  of  rabbits  with,  causing  paralysis,  78 

Striimpell,  cases  of  infantile  paralysis  in  Germany,  138 

— ,  connection  of  certain  forms  of  neuritis  with  poliomyelitis  by,  11 

— ,  etiology  of  epidemic  infantile  paralysis,  5,  23 


208  EPIDEMIC  INFANTILE  PARALYSIS 

Submaxillary  glands  in  monkeys,  poliomyelitis  virus  in,  q8 
Sweating,  excessive  in  prodromal  stage  of  Heine-Medin  disease,  14 
Sweden,  epidemics  of  Heine-Medin  disease  in,  136,  137,  141 
Switzerland,  cases  of  Heine-Medin  disease  in,   139 

Temperatures,  low  and  high,  effect  on  poliomyelitis  virus,  65,  66 

Thermana?sthesia  in  Heine-Medin  disease,  16 

Thymol,  effect  on  poliomyelitis  virus,  67 

Traestena  (Norway),  school  infection  of  Heine-Medin  disease  at,  1  j6 

Traffic,  spread  of  Heine-Medin  disease  along  lines  of,  137 

ULTRA-MICROSCOPE,  discovery  of  small,  rounded  bodies  under,  28 
United  States,  epidemics  of  Heine-Medin  disease  in,  140,  141 
Urotropin  in  Heine-Medin  disease,  173,  174 

VERMONT,    epidemic   of  infantile  paralysis   in,    140 
Virus  of  Heine-Medin  disease  (see  Poliomyelitis  virus) 

WEST,  C,  "  paralysis  of  the  morning,"'  term  proposed  by,  10 
Westphalia,  epidemic  of  Heine-Medin  disease  in  (1909),  26,  27,  138 
Wickman,     adoption    of    term    Heine-Medin    disease     for    spinal     infantile 

paralysis,  2 
— .  clinical  and  histological  studies  of  Heine-Medin  disease,   13 
— ,  contagiousness  of  Heine-Medin  disease,   146 
— ,  epidemics  of  Heine-Medin  disease  in  Sweden,  137 
— ,  epidemiology  of  infantile  paralysis,  5 
,  identity    of    Landry's    paralysis    and    certain    forms    of    myelitis     with 

poliomyelitis,  established  by,  04 
— ,  immunity  to  Heine-Medin  disease,  150 
— ,  microscopic    changes    in    brain    in    poliomyelitis    in    monkeys    and    man 

compared,  122,  123 
— ,  neuronophagy  of  spinal  ganglion  cells  in  poliomyelitis,   115-121 
— ,  pathology  and  pathogenesis  of  Heine-Medin  disease,  93,  94 
— ,  symptomatology  of  Heine-Medin  disease  in  man,  13,  14 

Zappert,  contagiousness  of  Heine-Medin  disease,  147 

— ,  immunity  to  Heine-Medin  disease,  149 

—    and  Neurath,  epidemic  of  Heine-Medin  disease  in  Austria.   138 


"V^G^ 


■  ^ 


. 


